The aim of this cross-sectional study is (1) to describe the socio-demographic characteristics of students with relatives with problematic substance use and to examine differences between students with and without relatives with problematic substance use in (2) health, (3) substance use and (4) study success. We analyzed these differences in bivariate analyses between 881 (15.6%) students in a Dutch university population with relatives with problematic substance use (referred to as Affected Family Members (AFMs) and 4,781 students without such relatives. AFMs reported poorer health and used more substances, especially cannabis, than did non-AFM students and drank more often alone than did their peers. AFMs had more frequently study delay and missed class more often because of drug use. AFMs with more than one relative with problematic substance use had poorer health than AFMs with only one relative. Effect sizes were small to moderate. Health and educational professionals should provide support to deal with difficult life circumstances, for example, trauma-informed care programs.