In this paper, optimum detection threshold for minimum bit error rate (BER) due to four-wave mixing is calculated taking the probability distribution of power depletion as binomial and considering nonuniform channel spacing. Nondegenerate four-wave mixing has been assumed for the worst-case analysis. The effects of the number of interfering channels, receiver noise, and input power on the BER in the presence of four-wave mixing are studied. The optimum detection threshold for minimum BER is studied as a function of the number of channels. This optimum threshold significantly deviates from the conventional threshold in the Gaussian distribution approximation as the channel number increases beyond three. © 2009-2012 OSA.