Mnemonic discrimination is the ability to discriminate among similar memories, which requires separable representations of similar information. The neurocomputational process that assumedly decorrelates representations during encoding and consolidation is referred to as pattern separation. Deficits in pattern separation contribute to age-related declines in mnemonic functioning, which has motivated the development of targeted interventions. We followed-up a recent report that one 200 mg-dose of caffeine administered post-study enhances mnemonic discrimination [Borota, D., Murray, E., Keceli, G., Chang, A., Watabe, J. M., Ly, M., Toscano, J. P., & Yassa, M. A. (2014). Post-study caffeine administration enhances memory consolidation in humans. Nature Neuroscience, 17(2), 201-203. https://doi.org/10.1038/nn.3623]. To test whether the reported enhancements are an artifact of performance-impairing withdrawal symptoms in the control group, we did not restrict preexperimental caffeine intake and statistically adjusted treatment effects for habitual caffeine consumption. We detected no effects of caffeine and nonsuperiority testing ruled out medium and large enhancements in both average (1200 mg per week) and low-consumers (50 mg per week). Our results raise doubts about a caffeine-mediated enhancement of mnemonic discrimination on two counts: If the effect exists, it (1) is substantially smaller than originally reported and (2) may reflect an offset of performance-impairing withdrawal symptoms rather than genuinely enhanced consolidation. We recommend that future studies employ an alternating exposure-abstinence protocol, use an active control group, and verify posttreatment caffeine abstinence via saliva or blood samples.