Revisiting this, I stand corrected from my earlier post, I note that in working on my star system simulator application the effect that never bugged me before, becomes more pronounced when you have occasion to use the wheel for fine control.
I recently added a mouse wheel zooming capability, whereby rolling the mouse one direction zooms in, while rolling the other way zooms out. Similar to applications such as various CAD aps and Blender. Additionally, clicking the mouse wheel returns to a default zoom factor. Each detent of the mouse wheel, or what I'll refer to as a "roll click", results in a halving or doubling of the zoom factor. Here is where the mouse action becomes most noticeable.
As Ophelius noted earlier, the precise behaviour seems to be that rolling the mouse wheel in one direction will yield the desired results. You can stop and then continue without any issues. However, reversing the mouse wheel direction will result in two "dry roll clicks" of the wheel, where nothing will happen in the application, and the desired effect will start on the third "roll click". Clicking the wheel as you would a button doesn't reset the behaviour in any way. For some reason QB64 chooses to ignore two wheel detents upon reversal.
I never thought much of it before, as it wasn't as noticeable in the IDE, given that I was rapidly rolling the wheel through large blocks of code and never had occasion for finer control.
I went to a Blender project I'm working on and it would not duplicate the effect, so it's obviously not a hardware or OS issue, unless its associated with certain individual systems and their interaction with the IDE. QB64 and its compiled applications seems to consistently lose two mouse wheel detents when reversing the wheel.