Asthma and obesity disproportionately affect US African-American youth. Among youth with asthma, obesity has been associated with poor control. The impact of gender on this association is unclear. We examined these relationships in a sample of urban, African-American adolescents with asthma. Questionnaires were used to identify high school students with asthma, and to examine the association of body mass index (BMI) to asthma morbidity, by gender. Of 5967 students completing questionnaires, 599 (10%) met criteria for asthma and 507 had data sufficient for inclusion in further analyses (46% male, mean age = 15.1 yr). Univariately, BMI > 85th percentile was significantly related only to reported emergency department visits (ED) and school days missed for any reason, Odds Ratio (95%Confidence Interval) = 1.7(1.1-2.7), p = 0.01 and 1.8(1.1-3.0), p = 0.01, respectively. A significant gender-BMI interaction (p < 0.05) was observed in multivariate models for ED visits, hospitalizations and school days missed for asthma. In gender-specific models, adjusted Risk Ratios for BMI > 85th and ED visits, hospitalizations, and school days missed because of asthma were 1.7(0.9-3.2), 6.6(3.1-14.6) and 3.6(1.8-7.2) in males. These associations were not observed in females. Gender modifies the association between BMI and asthma-related morbidity among adolescents with asthma. Results have implications for clinical management as well as future research.