Objectives The aim of the study was to assess insulin resistance parameters using successive homeostasis model assessment (HOMA) and clinical evaluations in healthy new users of depot medroxyprogesterone acetate (DMPA). Methods A prospective 12-month study was carried out to compare 31 DMPA users with 25 copper intrauterine device (Cu-IUD; TCu380A) users, matched for age (± 1 year) and body mass index (BMI; ± 1 kg/m(2)). Participants met the following criteria: age 18 to 40 years, BMI < 30 kg/m(2), fasting glucose < 5.5 mmol/l, 2-h glucose after a 75 g oral glucose load < 140 mg/dl. BMI, waist circumference, fasting glucose, fasting insulin and HOMA of insulin resistance (HOMA-IR) were evaluated at baseline and after 6 and 12 months of contraceptive use. Insulin resistance was defined as a HOMA-IR value > 2.7. Results The DMPA group showed significant increases in BMI, waist circumference, fasting insulin and HOMA-IR throughout the observation period in relation to baseline. Significant increases in BMI and waist circumference were observed in the DMPA group at 12 months compared with the Cu-IUD group. Five DMPA users had abnormal HOMA-IR values, three of whom had gained > 5 kg in weight at 12 months. Conclusions HOMA-IR represents a useful tool to indicate changes in carbohydrate metabolism in non-obese DMPA users, especially when accompanied by measurement of clinical parameters such as BMI and waist circumference.2122-29