Objective: To examine weight changes in a large cohort of obese and nonobese a dolescent girls initiating depot medroxyprogesterone acetate (DMPA), an oral con traceptive (OC), or no hormonal contraceptive method (control). Design, Setting, and Participants: Prospective study of 450 adolescent girls, aged 12 to 18 year s, who attended 4 urban health clinics and selected DMPA, OC, or control. Data c ollection occurred at baseline and at 6, 12, and 18 months; consisted of structu red interview and measurement of height and weight; and occurred from April 19, 2000, through September 26, 2003. Main Outcome Measure: Weight was examined as m ean change over 18 months and actual weight at each study visit. On the basis of preliminary analyses, we stratified the sample according to baseline obesity st atus (nonobese, body mass index [calculated as weight in kilograms divided by t h e square of height in meters] < 30; obese, body mass index ≥30 ). Results: Ado l escent girls who were obese at initiation of DMPA gained significantly more weight than did obese girls starting OC or control (P < .001 for both). At 18 months ,mean weight gain was 9.4, 0.2, and 3.1 kg for obese girls receiving DMPA, recei ving OC, and control, respectively. Weight gain in obese girls receiving DMPA wa s also greater than weight gain in all nonobese categories (4.0 kg, DMPA; 2.8 kg , OC; 3.5 kg, control; P < .001). A significant interaction (P=.006) between len gth of time receiving DMPA and weight gain was evident for obese subjects. Concl usions: Over 18 months, DMPA use was associated with increasing rates of weight gain in obese subjects. The potential contribution to severe obesity in this pop ulation is concerning. Objective: To examine weight changes in a large cohort of obese and nonobese a dolescent girls initiating depot medroxyprogesterone acetate (DMPA), an oral con traceptive (OC), or no hormonal contraceptive method (control). Design, Setting, and Participants: Prospective study of 450 adolescent girls, aged 12 to 18 year s, who attended 4 urban health clinics and selected DMPA, OC, or control. Data c ollection occurred at baseline and at 6, 12, and 18 months; consisted of structu red interview and measurement of height and weight; and occurred from April 19, 2000, through September 26, 2003. Main Outcome Measure: Weight was examined as m ean change over 18 months and actual weight at each study visit. On the basis of preliminary analyzes, we stratified the sample according to baseline obesity st atus (nonobese, body mass index [calculated as weight in kilograms divided by the square of height in meters] <30; obese, body mass index ≥30). Results: Adolescent girls who were obese at initiation of DMPA significantly more than than obese girls starting OC or control (P <.001 for both). At 18 months, mean weight gain was 9.4, 0.2, and 3.1 kg for obese girls receiving DMPA, recei ving OC, and control, respectively. Weight gain in obese girls receiving DMPA wa s greater than weight gain in all nonobese categories (4.0 kg, DMPA; 2.8 kg, OC; 3.5 kg, control; P <.001) .006) between len gth of time receiving DMPA and weight gain was evident for obese subjects. Concl usions: Over 18 months, DMPA use was associated with increasing rates of weight gain in obese subjects. The potential contribution to severe obesity in this pop ulation is concerning.