Hispanic individuals are underrepresented in clinical and research populations and are often excluded from clinical trials in the United States. Hence, there are few data on the effectiveness of most empirically validated therapies for Hispanic substance users. The authors conducted a multisite randomized trial comparing the effectiveness of 3 individual sessions of motivational enhancement therapy with that of 3 individual sessions of counseling as usual on treatment retention and frequency of substance use; all assessment and treatment sessions were conducted in Spanish among 405 individuals seeking treatment for any type of current substance use. Treatment exposure was good, with 66% of participants completing all 3 protocol sessions. Although both interventions resulted in reductions in substance use during the 4-week therapy phase, there were no significant Treatment Condition x Time interactions nor Site x Treatment Condition interactions. Results suggest that the individual treatments delivered in Spanish were both attractive to and effective with this heterogeneous group of Hispanic adults, but the differential effectiveness of motivational enhancement therapy may be limited to those whose primary substance use problem is alcohol and may be fairly modest in magnitude. (Contains 3 tables, 2 figures, and 1 footnote.)