Statins exert cholesterol-independent beneficial effects on multiple targets including the cardiovascular system, in addition to modulating matrix metalloproteinases (MMPs) expression. The purpose of this study was to assess the effects of simvastatin treatment in obese women without comorbidities. We recruited 33 obese women that received placebo or simvastatin at 20 mg/day for 45 days. Plasma MMP-9, MMP-2, TIMP-1, and TIMP-2 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Cardiovascular risk was assessed by the Framingham risk score and Castelli indexes I and II. Treatment with simvastatin significantly reduced MMP-9 levels and the MMP-9/TIMP-1 ratio (P < .05) when compared to the placebo group (P > .05). Conversely, we found no effect on MMP-2, TIMP-1, and TIMP-2 levels or on the MMP-2/TIMP-2 ratio (P > .05). The Framingham risk score and Castelli I and II indexes were significantly reduced in the simvastatin-treatment group (P < .05), while we found no effect on the placebo group. These findings may have clinical importance since simvastatin therapy reduced cardiovascular risk and MMP-9 levels in obese woman without comorbidities, indicating a potentially new therapeutic approach.