Depo-medroxyprogesterone Acetat is a long acting, injectable progesterone derivative contraceptive which is currently used by more than 90 million women worldwide. This contraceptive is suggested to induce changes in lipid profile, body weight and blood pressure among various populations and ethnic group with different patterns. The main objective of this study was to investigate the effects of use of DMPA on lipid profile, body weight and blood pressure of women attending family planning unit in Tekele Hymanot and Lomeda Health Centers, Addis Ababa, Ethiopia. Institutional based cross-sectional study design was followed on women attending the Health Centers between 14 February, 2015 and 13 March, 2015. Serum TC and LDL-c levels in DMPA users were significantly increased compared to controls, on the other hand, serum HDL-c level in DMPA users was significantly decreased compared to controls. Serum TG level in DMPA users was higher than control group. The mean weight and body mass index of DMPA users were increased significantly. There was no significant difference in MAP of DMPA users compared to controls or compared to their respective pretreatment value.