This study examined the multiple factors of protective behaviors, alcohol consumption, and harmful consequences in a sample of college students from four universities. It was hypothesized that students who use protective behaviors would be less likely to experience harmful consequences due to their drinking. Because of the potential mediating factors of gender and Greek organization membership, differences among these groups were also analyzed. The overall sample consisted of 3,782 students who completed the Campus Alcohol Survey during the 2000 spring semester. Only drinkers were considered in the analysis, resulting in a final sample of 3,185 students. Drinkers were analyzed by their level of protective behavior use, four measures of drinking, and types of harmful consequences. As expected, students who used protective behaviors drank less and experienced fewer harmful consequences from their drinking, and, the more protective behaviors they used, the stronger the effect. As a group, Greek males drank more, used fewer protective behaviors, and experienced more harmful consequences than non-Greek males, Greek females, or non-Greek females. However, the effect of gender was stronger than the effect of Greek membership. Female students generally used more protective behaviors, drank less, and experienced fewer consequences than did males. The results provide some support for the harm reduction approach to alcohol prevention and indicate a need for prevention programs that target Greeks and males. Additionally, protective behaviors can be promoted in media campaigns as a positive social norm among these college students.