College students with attention-deficit/hyperactivity disorder (ADHD) are at higher than average risk for alcohol and substance use; however, it is unclear whether having ADHD, either alone or in combination with other factors, increases this risk. Further, no prior studies have systematically examined factors that correlate with alcohol and substance use among college students with ADHD. A sample of first year college students with (n = 228; 52.2% female; 76.8% Caucasian) and without (n = 228; 51.3% female; 51.3% Caucasian) ADHD from 10 eastern US universities participated in a longitudinal study examining the long-term outcomes of college students with ADHD. Participants completed a battery of measures including self-report ratings of alcohol and substance use; ADHD, externalizing disorder, anxiety disorder, and depression symptoms; executive functioning; and learning and study strategies. First-year college students with ADHD were significantly more likely to use tobacco, cannabis, and illicit drugs (Cohen's d range = 0.30 to 0.33), but not alcohol (Cohen's d = 0.18). Separate multiple regression models indicated that each of the four substance use outcomes was best explained by a unique combination of predictive factors with anxiety symptoms and executive functioning deficits correlated with increased use of at least two of the substances. Additional longitudinal research is necessary to identify variables associated with ongoing substance use in college students with ADHD so as to inform screening, prevention, and intervention efforts.