A 14-week double blind study compared the efficacy of olanzapine to risperidone in reducing marijuana/cocaine craving and use in individuals with schizophrenia. The study consisted of three phases: a two-week assessment phase, a two-week cross-taper phase onto olanzapine/risperidone, and a ten-week period of maintenance on olanzapine/risperidone. The proportion of cocaine-positive urines decreases over time for both groups with a trend for a greater reduction for the olanzapine group compared to risperidone group. In the last six weeks, marijuana craving was more likely for the risperidone group compared to the olanzapine group, although there was no group difference in the proportion of negative marijuana urines. The data suggest some potential for the utility of olanzapine for the treatment of cocaine dependence in individuals with schizophrenia.