Let S be a fixed set of primes and let a 1 , . . . , a m denote distinct positive integers. We call the m-tuple (a 1 , . . . , a m ) an S-Diophantine tuple if the integers a i a j + 1 = s i,j are S-units for all i 6 = j. In this paper, we show that if S = {p, q} and p, q ⌘ 3 (mod 4), then no S-Diophantine quadruple exists.