You can have the formula in the second workbook and have it reference the first, certainly.

But I suppose it really depends on what you're going to do with that second workbook after the calculation. Maybe you'd still need VBA to make the looked up value static rather than the shown result of a formula.

My VBA knowledge isn't great so you may be better placed to decide if that would work for you or if a full VBA solution would be worth hanging on for.

Do you know of any formulas that will work for this? I added this into my post, but basically I need to lookup two values and return two values (as well as subtract them). I was playing with index and match, but I'm not having too much luck.

So you need to show three values (first, second and the difference between) for each combination in columns B & C?

I have a horrid feeling I'm completely misunderstanding what you're trying to achieve here... perhaps an example workbook would be a good idea?