Objective: Behavioral economic theory suggests that a reduction in alcohol use is most likely when there is an increase in rewarding substance-free activities. Anxiety has also been linked to heavy drinking, and strategies to reduce anxiety may enhance alcohol interventions. The goal of this 2-site randomized controlled clinical trial was to evaluate the efficacy of a brief alcohol intervention that was supplemented with either a behavioral economic substance-free activity session (SFAS) or a relaxation training (Relaxation training RT) session. Method: Participants were 393 college students (61% female, mean age = 18.77 years) who reported 2 or more past-month heavy drinking episodes. Participants were randomized to 1 of 3 conditions: (a) assessment; (b) alcohol brief motivational intervention (BMI) plus SFAS; or (c) BMI plus RT. Both treatment conditions included 2 in-person sessions plus a phone booster session. Outcomes were evaluated 1-, 6-, 12-, and 16-months postintervention. Results: Generalized linear mixed models indicated that the combination of a BMI plus either the SFAS or RT was associated with significant reductions in alcohol use and problems across the 16-month follow-up compared with assessment only. There were no significant differences between the two active treatment conditions. Changes in proportional reinforcement from substance-related activities, and protective behavioral strategies mediated treatment effects. Conclusion: Two-session (plus booster) interventions that combine BMI and either substance-free activity enhancement or RT can result in enduring reductions in alcohol misuse among college drinkers. What is the public health significance of this article? Heavy drinking among college students is a significant public health concern. Brief alcohol interventions are effective, but drinking reductions are generally small, suggesting the need for additional intervention elements. The results of this randomized clinical trial suggest that brief alcohol interventions that are supplemented with either relaxation training or a behavioral economic session focused on increasing substance-free activities are associated with reductions in alcohol misuse over a 16-month follow-up period.