Previous research on the association between intra-subject variability (ISV) in reaction times (RTs) and the Val158Met polymorphism of the catechol-o-methyltransferase gene (COMT; rs4680) has yielded mixed results. The present study compared the associations between COMT genotype and ISV in P3b latency measured during working and secondary memory tasks using residue iteration decomposition (RIDE) of single trial latencies. We compared the outcome of the present analyses with a previous analysis of the same data (N = 70, n-back tasks) using an alternative single-trial method. Additionally, we used RIDE to analyse the association between COMT genotype and ISV in an independent sample performing a different task (N = 91, face-recognition task). Analyses reconfirmed previous results from the n-back tasks, showing that Val alleles are associated with lower ISV. In the face recognition tasks, genotype interacted with task conditions, so Val homozygotes had higher ISV to unfamiliar faces than familiar ones but Met carriers showed no effect of familiarity. Moreover, in both datasets trial-by-trial RTs were predicted by P3b latencies. Therefore, the present data suggests that associations between COMT genotype and ISV depend on the type of cognitive processes, which may explain heterogeneity in previous results.