The purpose of this study was to examine the effects of two incentive conditions (a $10 pre-incentive only vs. a $2 pre-incentive and a $10 promised incentive) on response rates, sample composition, substantive data, and cost-efficiency in a survey of college student substance use and related behaviors. Participants were 3000 randomly-selected college students invited to participate in a survey on substance use. Registrar data on all invitees was used to compare response rates and respondents, and web-based data collection on participants was used to compare substantive findings. Participants randomized to the pre-incentive plus promised incentive condition were more likely to complete the survey and less likely to give partial responses. Subgroup differences by sex, class year, and race were evaluated among complete responders, although only sex differences were significant. Men were more likely to respond in the pre-incentive plus promised incentive condition than the pre-incentive only condition. Substantive data did not differ across incentive structure, although the pre-incentive plus promised incentive condition was more cost-efficient. Survey research on college student populations is warranted to support the most scientifically sound and cost-efficient studies possible. Although substantive data did not differ, altering the incentive structure could yield cost savings with better response rates and more representative samples.