Osteoporosis (OP) has been associated with cardiovascular disease. More specifically, osteoporosis was found to be an independent predictor of cardiovascular mortality. Recent studies revealed that platelets play a critical role in bone remodeling. Mean platelet volume (MPV) is an early marker of platelet activation, which is involved in the pathophysiology of coronary heart disease. However, little research has been conducted to investigate the relationship between MPV and OP. In this cross-sectional study, we investigated the relationship between platelet count, MPV, and bone mineral density (BMD) in 410 subjects in the geriatric department of the Second Affiliated Hospital, Harbin, China. Different biochemical parameters, platelet count, and MPV were determined, and bone mineral density (BMD) (g/cm(2)) was measured in the osteoporosis, osteopenia, and normal BMD groups. Mean age, systolic blood pressure (SBP), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), and MPV increased gradually, and body mass index (BMI), decreased as BMD decreased. A negative correlation was present between MPV and the lumbar spine (L2-L4) and femoral neck BMD after adjusting other risk factors. Univariate analysis and multivariate analysis showed that MPV was significantly associated with lumbar spine L2-L4 BMD and femoral neck BMD (β = -0.285, P < 0.001 for lumbar spine L2-L4 BMD; β = -0.207, P < 0.001 for femoral neck BMD in multivariate model). The findings show that MPV is negatively correlated with BMD. Further studies on the involvement of MPV in osteoporosis may contribute to the evaluation of thrombotic risk in elderly patients with osteoporosis.