Little is known about the association between self-reported academic performance and risky sexual behaviors and if this differs by gender, among university students. Academic performance can create psychological pressure in young students. Poor academic performance might thus potentially contribute to risky sexual behavior among university students. The aim of this study was to investigate the association between self-reported academic performance and risky sexual behaviors, and whether gender affects this relationship among Ugandan university students. In 2010, 1,954 students participated in a cross-sectional survey, conducted at Mbarara University of Science and Technology in southwestern Uganda (72% response rate). Multivariate logistic regression analysis was used for the analysis. 1,179 (60.3%) students in our study sample reported having debuted sexually. Of these 440 (42.2%) used condoms inconsistently with new sexual partners, and 344 (33.6%) had had multiple sexual partners. We found a statistically significant association between poor academic performance and inconsistent condom use with a new sex partner and this association remained significant even after adjusting for all the potential confounders. There was no such association detected regarding multiple sexual partners. We also found that gender modified the effect of poor academic performance on inconsistent condom use. Females, who were poor academic performers, were found to be at a higher risk of inconsistent condom use than their male counterparts. Interventions should be designed to provide extra support to poor academic performers, which may improve their performance and self-esteem, which in turn might reduce their risky sexual behaviors.