While alcohol remains the drug of choice for most college students, national data show that 40% of college students also use other substances (e.g., marijuana, cocaine, etc.). Longitudinal studies indicate that students who report use of both alcohol and other substances experience more consequences (e.g., blackout, arrests). The current study expands upon this research by using a multilevel approach to examine average and event-level alcohol combined with other substance use (ALC+) and its role on consequences experienced. In addition, the research examined which substance combined with alcohol posed the most risk. A total of 461 students reported on alcohol use, substance use, and consequences experienced (e.g., Young Adult Alcohol Consequences Questionnaire [YAACQ]) on 12 weekend nights (Thursday, Friday, Saturday) across 4 weekends in an academic year. Multilevel model analyses revealed a positive association between both average and event-level ALC+ use and the number of consequences experienced. A significant cross-level interaction was also revealed indicating students who typically combine alcohol and other substances experienced more consequences on occasions when they use more substances relative to students who typically use alcohol only. Finally, alcohol plus nicotine, or marijuana, or attention-deficit/hyperactivity disorder (ADHD) medications, or cocaine were all significantly positively related to increased consequences. These findings provide consistent evidence that ALC+ use is a highly prevalent behavior among college students that increases risk of problematic consequences.