Background University students’ substance abuse and risky sex contribute to sexually transmitted diseases (STDs). Purpose We develop and empirically test a formative theoretical model of sexual temptation involving substance abuse (cigarettes, alcohol, and marijuana), safe sexual behavior (use of condom/barrier for oral and vaginal intercourse), risky sexual behavior (unprotected sex and multiple sexual partners), and STDs: gonorrhea, HIV, and genital herpes. We simultaneously explore these constructs, controlling membership in social groups (fraternity/sorority, varsity athlete, and club sports) and perceived norm of substance abuse. Methods A total of 687 American university students completed the National College Health Assessment (NCHA). We use structural equation modeling (SEM) to test the goodness of fit between our formative theoretical model and actual data. Results Results reveal the following discoveries: membership in campus social groups is positively associated with STDs, whereas perceived norm of peer substance abuse is negatively related to STDs. Under the influence of substance abuse, we test three outcomes of sexual temptation as related to STDs. Those who have no sex do not contract STDs. For those who fall into temptation and have sex, substance abuse is more strongly related to risky sex which leads to STDs than safe sex which does not. Those engaging in risky sex have significantly higher cognitive impairment than those practicing safe sex. Conclusions Substance abuse contributes to STDs through risky sex only. Those having risky sex suffer higher cognitive impairment than those practicing safe sex. We provide novel implications to policy makers, practitioners, and researchers.