Aim The aim of this study was to assess the effects of the injectable depot-medroxyprogesterone acetate (DMPA) contraceptive on selected blood coagulation parameters in young, healthy new users. Methods The prospective study included 39 healthy women aged 20-39 years, with a body mass index (BMI; kg/m2) < 30, who were never users of DMPA, and who opted to use DMPA (21 women) or a copper intrauterine device (IUD; 18 women). The women in the two groups were matched for age (±1 year) and BMI (±1). Blood samples were obtained from all participants at baseline and at 6 and 12 months. Activated partial thromboplastin time, D-dimer, protein C, antithrombin, protein S, and thrombin generation test (lag time, endogenous thrombin potential, time to peak, and velocity index of thrombin generation) were analyzed. Repeated-measures analysis of variance was used to compare the groups. Results There were no significant differences between the groups at baseline with respect to any of the parameters evaluated; however, in the DMPA group, D-dimer levels were lower and the time to peak thrombin generation was longer than in the IUD group at 12 months of evaluation. Conclusion Lower D-dimer and longer time to peak thrombin generation in new users of DMPA suggest a positive profile against hypercoagulability. [ABSTRACT FROM AUTHOR]