OBJECTIVE: Few studies examining the relationship between obesity and health-related quality of life (HRQOL) have used a medical outpatient population or demonstrated a relationship in men. Furthermore, most studies have not adequately considered comorbid illness. The goal of this study was to examine the relationship between body mass index (BMI) and HRQOL in male outpatients while considering comorbid illness. RESEARCH METHODS AND PROCEDURES: This cross-sectional study examined 1168 male outpatients from Durham Veterans' Affairs Medical Center. Multiple linear regression was used to examine the relationship of BMI with each subscale from the Medical Outcomes Study Short Form 36 while adjusting for age, race, comorbid illness, depression, and physical activity. RESULTS: Participants had a mean age of 54.7 +/- 5.6 years; 69% were white and 29% were African American. The distribution for BMI was as follows: 18.5 to <25 kg/m(2) (21%), 25 to <30 kg/m(2) (43%), 30 to <35 kg/m(2) (25%), 35 to <40 kg/m(2) (8%), and > or =40 kg/m(2) (3%). Mean Short Form 36 subscale scores were lower than U.S. norms by an average of 27%. Individuals with BMI > or =40 kg/m(2) had significantly lower scores compared with normal weight individuals on the Role-Physical and Vitality subscales. On the Physical Functioning and Physical Component subscales, lower scores were observed at BMI > or =35 kg/m(2). On the Bodily Pain subscale, lower scores were observed at BMI > or =25 kg/m(2). DISCUSSION: An inverse relationship between BMI and physical aspects of HRQOL exists in a population of male outpatients. Increased BMI was most prominently associated with bodily pain; this relationship should receive more attention in clinical care and research.