Recent preclinical studies implicate N-acetylcysteine (NAC), a cysteine prodrug, as a potential medication for preventing relapse to cocaine use; however, little is known about the safety and tolerability of NAC in cocaine-dependent subjects in an outpatient setting. This pilot study examines the safety and tolerability of 3 doses of NAC for the treatment of cocaine dependence. Twenty three treatment-seeking cocaine-dependent patients participated in a 4-week medication trial and received NAC at doses of 1200 mg/day, 2400 mg/day or 3600 mg/day. Results suggested that the three doses were well tolerated. Overall, the retention rates appeared to favor higher doses of NAC (2400 mg/day and 3600 mg/day). The majority of subjects who completed the study (n=16) either terminated use of cocaine completely or significantly reduced their use of cocaine during treatment. Overall the findings suggest that it is feasible to treat cocaine-dependent treatment seekers with N-acetylcysteine on an outpatient basis.