Background. Psychological stress has been linked in some studies to asthma prevalence and outcomes in children. The authors sought to evaluate the relationship between perceived stress and morbidity among inner-city adults with asthma. Methods. The authors interviewed a prospective cohort of 326 moderate-to-severe asthmatics receiving care at two large, urban, hospital-based general medicine clinics in New York City and New Jersey. Psychological stress was assessed at baseline using the Perceived Stress Scale (PSS), a validated 4-item instrument. Outcomes included the Asthma Control Questionnaire (ACQ), the Asthma Quality of Life Questionnaire (AQLQ), and the Medication Adherence Reporting Scale (MARS) measured at baseline, 1, 3, and 12 months of enrollment. Results. Higher perceived stress was significantly correlated with worse asthma control (ACQ scores; r = .30 to .37, p < .0001), poor quality of life (AQLQ scores; r = -.49 to - .35, p < .0001), and decreased medication adherence (MARS scores; r = -.25 to -.15, p < .028) at baseline and across the follow-up interviews. In multivariate analyses, increased stress remained a significant predictor of worse ACQ (p < .0001), AQLQ scores (p < .0001), and MARS (p < .0001) after adjusting for age, sex, income, number of years with asthma, and comorbidities. Conclusions. Among inner-city asthmatics, higher perceived stress is strongly associated with increased asthma morbidity across a 1-year follow-up. Further research is needed to identify mechanisms mediating the association between stress and asthma morbidity in adults.