Smoking cocaine achieves maximal concentration and effect far more rapidly than through the intranasal (‘snorting’) route, and it is associated with greater propensity for dependence and more severe consequences. However, very little is known about differences in treatment outcome according to route of administration. This study compared treatment outcomes, such as frequency of cocaine use and Addiction Severity Index (ASI) composite scores, by primary route of cocaine administration (smoking vs. intranasal) among a pooled sample of 412 cocaine-dependent individuals participating in one of five randomized clinical trials. The majority (80%) reported smoking as their primary route of cocaine administration. Overall, results indicated better cocaine use outcomes both during the treatment phase and through a 12-month follow-up period for intranasal users compared to smokers, although not all differences reached statistical significance. Intranasal users remained in treatment longer [F(1,408) = 3.55, p < .05], and showed a trend toward achieving longer periods of sustained abstinence within treatment [F(1,378) = 2.68, p = .08], as well as less use over time during the follow-up period than smokers (Time x Route: t = 1.87, p = .06). Also, intranasal users’ ASI cocaine composite score decreased more than smokers, but there were overall decreases in the other ASI domains for all participants over the course of the study period. These results suggest that intranasal users may achieve better cocaine use outcomes than smokers, yet this doesn't appear to translate to differential changes in the severity of problems experienced in other life areas.