Background: Concurrent alcohol and cannabis (i.e. marijuana) use (CAM; use of both substances within the same specified time frame) is prevalent among college students and associated with increased risk of negative substance-related consequences. Extant research supports the use of protective behavioral strategies (PBS) for reducing negative consequences associated with both alcohol and cannabis use. However, limited research exists regarding the efficacy of PBS among CAM users, and it is unknown whether using PBS for both alcohol and cannabis augments protective effects. The present study tested four moderation models to evaluate the interactive effects of alcohol and cannabis PBS on alcohol and cannabis negative consequences and use frequency. Methods: A multisite sample of college students (N = 1705) reporting past-month CAM use completed questionnaires regarding substance use behaviors, PBS use, and substance-related negative consequences. Results: Alcohol and cannabis PBS were negatively associated with alcohol and cannabis use, respectively. However, two-way interactions between PBS on substance use were not supported, such that negative associations between PBS and same-substance use were not augmented as other-substance PBS use increased. Interactive effects of alcohol and cannabis PBS on negative alcohol and cannabis consequences were supported, such that negative associations between alcohol PBS and consequences were augmented as cannabis PBS increased and vice versa. Conclusions: Findings suggest that using both types of PBS may increase protective effects against negative consequences among CAM users. Accordingly, promoting both types of PBS may enhance extant harm reduction interventions.