Background: Cross-sectional studies have demonstrated gender-related differences in the associations between problem-gambling severity and substance-use disorders; however, these associations have not been examined longitudinally. We aimed to examine the prospective associations between problem-gambling severity and incident substance-use disorders in women versus men. Methods: Analyses were conducted using Wave-1 and Wave-2 NESARC data focusing on psychiatric diagnoses from 34,006 non-institutionalized US adults. Inclusionary criteria for pathological gambling were used to categorize Wave-1 participants as at-risk/problem gambling (ARPG) and non-ARPG (i.e. non-gambling/low-frequency gambling/low-risk gambling). Dependent variables included the three-year incidence of any substance-use disorder, alcohol-use disorders, nicotine dependence, drug-use disorders, prescription drug-use disorders, and illicit drug-use disorders. Results: Significant gender-by-ARPG status interactions were observed with respect to the three-year incidence of nicotine dependence and prescription drug-use disorders, and approached significance with respect to incident alcohol-use disorders. ARPG (relative to non-ARPG) was positively associated with nicotine dependence among women (OR=2.00; 95% CI=1.24-3.00). ARPG was negatively associated with incident prescription drug-use disorders among men (OR=0.30; 95% CI=0.10-0.88)). Finally, ARPG was positively associated with incident alcohol-use disorders among men (OR=2.20; 95% CI=1.39-3.48). Conclusions: Gambling problems were associated with an increased 3-year incidence of nicotine dependence in women and alcohol dependence in men. These findings highlight the importance of considering gender in prevention and treatment initiatives for adults who are experiencing gambling problems. Moreover, the specific factors underlying the differential progressions of specific substance-use disorders in women and men with ARPG warrant identification.