To clear the immediate window, you can use >cls, which is a predefined command alias to >Edit.ClearAll.

The MSDN article lists all predefined aliases and you can define your own, too. (For VS 2010 and earlier, custom aliases are described in a separate article, though.) Scanning through, there's a whole slew of them, some of which might even have their roots in MS-DOS DEBUG.EXE (specifically >d, >g, >p, >q, and >t come to mind).

Also worth noting as it's only two keys to press: Context menu > Clear All invokes the same command and it can be navigated using keyboard. Therefore in the immediate window, you can press Context Menu, L.

If you don't have a context-menu key on your keyboard (you know, the one between Right Alt and Right Ctrl), you can use Shift+F10 instead.

>cls 

seems to do it for me.

found it...

">Edit.ClearAll"

or

">cls"

Here is how to do it at run time:

1. Reference the EnvDTE dlls in your application.

2. Create and then use this function as necessary.

Public Sub ClearImmediateWindow()
  Try
    Dim vsWindowKindImmediateWindow As String _ 
          = "{ECB7191A-597B-41F5-9843-03A4CF275DDE}"
    Try
      Dim obj As Object = System.Runtime.InteropServices.Marshal._ 
                          GetActiveObject("VisualStudio.DTE.10.0")
      If obj IsNot Nothing Then
        Dim DTE2 As EnvDTE80.DTE2 = CType(obj, EnvDTE80.DTE2)
        For Each wndw As EnvDTE.Window In DTE2.Windows
          If wndw.ObjectKind = vsWindowKindImmediateWindow Then
            wndw.Activate()
            DTE2.ExecuteCommand("Edit.ClearAll")
            Exit For
          End If
        Next
      End If
    Catch comEx As COMException
      ' Not running from within the VS IDE?
    Catch ex As Exception
      Throw ex
    End Try
  Catch ex As Exception
    ' Handle this as you desire.
  End Try
End Sub
  End Sub

I used the last answer just about verbatim and it works, although I wanted the focus back on where it was. Here's the very slightly improved C# version. I enable it with a configuration switch.

#if DEBUG
    if (GetIni("Debug", "ClearImmediateWindow", true)) {
        try {
            var dte = (EnvDTE.DTE) Marshal.GetActiveObject("VisualStudio.DTE.15.0");
            var me  = dte.ActiveWindow;
            dte.Windows.Item("Immediate Window").Activate();
            dte.ExecuteCommand("Edit.ClearAll");
            me.Activate();
        }
        catch { /* Meh! */ }

endif

Those who are wondering how to clear immediate window on Visual Studio Mac, just right click inside the window and select the option Clear