The objective of this study is to compare neuropsychological test performance before and after HIV-1 seroconversion in order to identify possible acute changes in psychomotor speed, memory, attention, and concentration secondary to seroconversion. The study utilized mixed effects models to examine longitudinal neuropsychological test data. We conducted a nested cohort study of 362 male HIV-1 seroconverters enrolled in the Multicenter AIDS Cohort Study. We used linear mixed models with random subject effects to compare repeated neuropsychological test outcomes from 5 years before seroconversion to 2 years after seroconversion on the Trail Making Test (parts A and B), Symbol-Digit Test, Grooved Pegboard (dominant and non-dominant hands), Stroop Color-Interference Test, Rey Auditory Verbal Learning Test, and the CalCAP Reaction Time Test. We found no significant changes in the time-dependent score after seroconversion for the majority of neuropsychological tests used in the Multicenter AIDS Cohort Study. There was a significant change in time trend after seroconversion on part B of the Trail Making Test (p = 0.042), but the difference only represented a 2 % decrease in performance. We found the following characteristics to be associated with worse neuropsychological test performance: lower education levels, history of depression, older age, and no previous neurocognitive testing (p < .05). Our results suggest that despite a 50 % decrease in CD4 cell count immediately following infection, HIV-1 does not appear to have a measurable effect on psychomotor or complex cognitive processing for up to 2 years following infection, using this set of neurocognitive measures.