Studies investigating carbamazepine (CBZ) in the treatment of cocaine dependence have been inconsistent. In this study, cocaine-dependent individuals with (n = 57) and without (n = 82) affective disorder were compared in a 12-week, double-blind, placebo-controlled trial. Urine drug screens (UDS) and self-report of drug use were collected weekly. Affective symptoms were measured monthly. Subjects receiving CBZ attended more medication sessions (p = .03). The CBZ-treated affective group had a trend toward fewer cocaine-positive UDS (p = .08) and a significantly longer time to first cocaine use (p = .06). CBZ treatment did not have any impact on cocaine use in individuals without affective disorders.