Do you mean by "4 full columns of data" that you have data from row 1 to row
65536 in columns A to D? (If so, RD's SP formula couldn't be used). Is the
data in some kind of sequence, or randomly distributed? Can it be sorted (so
a binary search could be used)?

I have read somewhere that MATCH is quicker to calculate than VLOOKUP, but
I've not tested this out.

Pete