这里有一个解决方案:

Protected Overrides Sub OnStartup(e As StartupEventArgs)
    Const appName As String = "TestApp"
    Dim createdNew As Boolean
    _mutex = New Mutex(True, appName, createdNew)
    If Not createdNew Then
        'app is already running! Exiting the application
        MessageBox.Show("Application is already running.")
        Application.Current.Shutdown()
    End If
    MyBase.OnStartup(e)
End Sub

简单地使用一个StreamWriter，怎么样?

System.IO.File.StreamWriter OpenFlag = null;   //globally

and

try
{
    OpenFlag = new StreamWriter(Path.GetTempPath() + "OpenedIfRunning");
}
catch (System.IO.IOException) //file in use
{
    Environment.Exit(0);
}

下面是一个示例，它允许您拥有应用程序的单个实例。当加载任何新实例时，它们将参数传递给正在运行的主实例。

public partial class App : Application
{
    private static Mutex SingleMutex;
    public static uint MessageId;

    private void Application_Startup(object sender, StartupEventArgs e)
    {
        IntPtr Result;
        IntPtr SendOk;
        Win32.COPYDATASTRUCT CopyData;
        string[] Args;
        IntPtr CopyDataMem;
        bool AllowMultipleInstances = false;

        Args = Environment.GetCommandLineArgs();

        // TODO: Replace {00000000-0000-0000-0000-000000000000} with your application's GUID
        MessageId   = Win32.RegisterWindowMessage("{00000000-0000-0000-0000-000000000000}");
        SingleMutex = new Mutex(false, "AppName");

        if ((AllowMultipleInstances) || (!AllowMultipleInstances && SingleMutex.WaitOne(1, true)))
        {
            new Main();
        }
        else if (Args.Length > 1)
        {
            foreach (Process Proc in Process.GetProcesses())
            {
                SendOk = Win32.SendMessageTimeout(Proc.MainWindowHandle, MessageId, IntPtr.Zero, IntPtr.Zero,
                    Win32.SendMessageTimeoutFlags.SMTO_BLOCK | Win32.SendMessageTimeoutFlags.SMTO_ABORTIFHUNG,
                    2000, out Result);

                if (SendOk == IntPtr.Zero)
                    continue;
                if ((uint)Result != MessageId)
                    continue;

                CopyDataMem = Marshal.AllocHGlobal(Marshal.SizeOf(typeof(Win32.COPYDATASTRUCT)));

                CopyData.dwData = IntPtr.Zero;
                CopyData.cbData = Args[1].Length*2;
                CopyData.lpData = Marshal.StringToHGlobalUni(Args[1]);

                Marshal.StructureToPtr(CopyData, CopyDataMem, false);

                Win32.SendMessageTimeout(Proc.MainWindowHandle, Win32.WM_COPYDATA, IntPtr.Zero, CopyDataMem,
                    Win32.SendMessageTimeoutFlags.SMTO_BLOCK | Win32.SendMessageTimeoutFlags.SMTO_ABORTIFHUNG,
                    5000, out Result);

                Marshal.FreeHGlobal(CopyData.lpData);
                Marshal.FreeHGlobal(CopyDataMem);
            }

            Shutdown(0);
        }
    }
}

public partial class Main : Window
{
    private void Window_Loaded(object sender, RoutedEventArgs e)
    {
        HwndSource Source;

        Source = HwndSource.FromHwnd(new WindowInteropHelper(this).Handle);
        Source.AddHook(new HwndSourceHook(Window_Proc));
    }

    private IntPtr Window_Proc(IntPtr hWnd, int Msg, IntPtr wParam, IntPtr lParam, ref bool Handled)
    {
        Win32.COPYDATASTRUCT CopyData;
        string Path;

        if (Msg == Win32.WM_COPYDATA)
        {
            CopyData = (Win32.COPYDATASTRUCT)Marshal.PtrToStructure(lParam, typeof(Win32.COPYDATASTRUCT));
            Path = Marshal.PtrToStringUni(CopyData.lpData, CopyData.cbData / 2);

            if (WindowState == WindowState.Minimized)
            {
                // Restore window from tray
            }

            // Do whatever we want with information

            Activate();
            Focus();
        }

        if (Msg == App.MessageId)
        {
            Handled = true;
            return new IntPtr(App.MessageId);
        }

        return IntPtr.Zero;
    }
}

public class Win32
{
    public const uint WM_COPYDATA = 0x004A;

    public struct COPYDATASTRUCT
    {
        public IntPtr dwData;
        public int    cbData;
        public IntPtr lpData;
    }

    [Flags]
    public enum SendMessageTimeoutFlags : uint
    {
        SMTO_NORMAL             = 0x0000,
        SMTO_BLOCK              = 0x0001,
        SMTO_ABORTIFHUNG        = 0x0002,
        SMTO_NOTIMEOUTIFNOTHUNG = 0x0008
    }

    [DllImport("user32.dll", SetLastError=true, CharSet=CharSet.Auto)]
    public static extern uint RegisterWindowMessage(string lpString);
    [DllImport("user32.dll")]
    public static extern IntPtr SendMessageTimeout(
        IntPtr hWnd, uint Msg, IntPtr wParam, IntPtr lParam,
        SendMessageTimeoutFlags fuFlags, uint uTimeout, out IntPtr lpdwResult);
}

这么简单的问题有这么多答案。稍微改变一下这里是我对这个问题的解决方案。

Creating a Mutex can be troublesome because the JIT-er only sees you using it for a small portion of your code and wants to mark it as ready for garbage collection. It pretty much wants to out-smart you thinking you are not going to be using that Mutex for that long. In reality you want to hang onto this Mutex for as long as your application is running. The best way to tell the garbage collector to leave you Mutex alone is to tell it to keep it alive though out the different generations of garage collection. Example:

var m = new Mutex(...);
...
GC.KeepAlive(m);

我从这个网页上获得了灵感:http://www.ai.uga.edu/~mc/SingleInstance.html

永远不要使用命名互斥来实现单实例应用程序(至少在生产代码中不要这样做)。恶意代码可以很容易地DoS(拒绝服务)你的屁股…

下面是我使用的一个轻量级解决方案，它允许应用程序将一个已经存在的窗口带到前台，而无需求助于自定义窗口消息或盲目地搜索进程名。

[DllImport("user32.dll")]
static extern bool SetForegroundWindow(IntPtr hWnd);

static readonly string guid = "<Application Guid>";

static void Main()
{
    Mutex mutex = null;
    if (!CreateMutex(out mutex))
        return;

    // Application startup code.

    Environment.SetEnvironmentVariable(guid, null, EnvironmentVariableTarget.User);
}

static bool CreateMutex(out Mutex mutex)
{
    bool createdNew = false;
    mutex = new Mutex(false, guid, out createdNew);

    if (createdNew)
    {
        Process process = Process.GetCurrentProcess();
        string value = process.Id.ToString();

        Environment.SetEnvironmentVariable(guid, value, EnvironmentVariableTarget.User);
    }
    else
    {
        string value = Environment.GetEnvironmentVariable(guid, EnvironmentVariableTarget.User);
        Process process = null;
        int processId = -1;

        if (int.TryParse(value, out processId))
            process = Process.GetProcessById(processId);

        if (process == null || !SetForegroundWindow(process.MainWindowHandle))
            MessageBox.Show("Unable to start application. An instance of this application is already running.");
    }

    return createdNew;
}

编辑:你也可以静态地存储和初始化互斥量和createdNew，但是一旦你完成了它，你需要显式地释放/释放互斥量。就我个人而言，我更喜欢将互斥锁保持在本地，因为即使应用程序在未到达Main结束时就关闭，它也会被自动销毁。