Use Win32::Process. It's the only way I've found to reliably do this. You can check my script, Perl/Tk Chatterbox Client, which employs this technique. Essentially, you create a new detached process. For example,

use Win32::Process;
Win32::Process::Create($Process, 
        "c:\\winnt\\system32\\notepad.exe",
        "notepad",
        0,
        DETACHED_PROCESS,
        ".") || die "Create: $!";
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Cheers,
Shendal