Cocaine abuse among HIV patients is associated with faster disease progression and mortality. This study examined the relationship between neurocognitive functioning and medication adherence in HIV patients with (n = 25) and without (n = 39) current cocaine dependence. Active users had greater neurocognitive impairment (mean T-score = 35.16 vs. 40.97, p < .05) and worse medication adherence (mean z-score = -0.44 vs. 0.27, p < .001). In a multiple regression model, neurocognitive functioning (β = .33, p < .01) and cocaine dependence (β = -.36, p < .01) were predictive of poorer adherence. There was a significant indirect effect of cocaine dependence on medication adherence through neurocognitive impairment (estimate = -0.15, p < .05), suggesting that neurocognitive impairment partially mediated the relationship between cocaine dependence and poorer adherence. These results confirm that cocaine users are at high risk for poor HIV outcomes and underscore the importance of treating both neurocognitive impairment and cocaine dependence among HIV patients.