Introduction:Osteoporosis (OP) is a major health problem in the older population. The aim of the study was to assess the role of serum osteoprotegerin (OPG) as a diagnostic indicator of primary osteoporosis in peri- and postmenopausal women in an Indian population. Materials and Methods: After ethical approval, 90 cases (45 cases and 45 controls) of peri- and post-menopausal females above 40 years of age presenting to our outpatient department were included in the study. It was a case controlled study conducted between July 2014 to July 2015. Based on the clinical features, t-score and radiological evidence from the DEXA scan, they were equally divided into two groups (cases and controls). Serum osteoprotegerin (OPG) levels were measured amongst cases and controls. Results:The total calcium (mg/dl) level was lower among the cases and the difference was significant (p-Value= <0.001). Similarly, alkaline phosphatase (u/l), osteoprotegerin (u/ml) levels were higher in the cases as compared to controls and the difference was significant (p-Value= <0.001). The mean osteoprotegerin level showed a slight increase with increase in severity of the grading of BMD of spine. The results suggested a cut-off value of ≥10.5 u/ml (86.7% sensitive and 80% specific with accuracy of 84.5%) between normal and osteoporosis. Conclusion: From the present study, we conclude that osteoprotegerin is a valid biomarker to diagnose postmenopausal women with low bone mineral density.