Objective: While research has documented heavy drinking practices and associated negative consequences of college students turning 21, few studies have examined prevention efforts aimed at reducing high-risk drinking during 21st birthday celebrations. The present study evaluated the comparative efficacy of a general prevention effort (i.e., Brief Alcohol Screening and Intervention for College Students, or BASICS) and event-specific prevention in reducing 21st birthday drinking and related negative consequences. Furthermore, this study evaluated inclusion of peers in interventions and mode of intervention delivery (i.e., in-person vs. via the Web). Method: Participants included 599 college students (46% male): men who intended to consume at least 5 drinks and women who intended to consume at least 4 drinks on their 21st birthday. After completing a screening/baseline assessment approximately 1 week before turning 21, participants were randomly assigned to 1 of 6 conditions: 21st birthday in-person BASICS, 21st birthday web BASICS, 21st birthday in-person BASICS plus friend intervention, 21st birthday web BASICS plus friend intervention, BASICS, or an attention control. A follow-up assessment was completed approximately 1 week after students' birthdays. Results: Results indicated a significant intervention effect for BASICS in reducing blood alcohol content reached and number of negative consequences experienced. All 3 in-person interventions reduced negative consequences experienced. Results for the web-based interventions varied by drinking outcome and whether a friend was included. Conclusions: Overall, results provide support for both general intervention and ESP approaches across modalities for reducing extreme drinking and negative consequences associated with turning 21. These results suggest there are several promising options for campuses seeking to reduce both use and negative consequences associated with 21st birthday celebrations. (Contains 1 figure and 4 tables.)