The literature on risk factors of osteoporosis in Saudi women is scarce and has several methodological limitations. This study aimed to assess the risk factors of osteoporosis among Saudi women in Qassim region of Saudi Arabia. An institution-based case-control study was conducted among women diagnosis of osteoporosis based on DEXA scan. Cases were recruited from regional DEXA scanning center of Qassim while controls were women visiting primary health care center. Data was collected using a structured questionnaire which collected information on socio-demographic and menopause and medical history. Analysis was done on SPSS version 23.0. Logistic regression was used to assess the risk factors and crude and adjusted odds ratio along with their associated 95% confidence intervals (CI) were calculated. A total of 115 cases and 183 controls were included in the analyses. The mean age of cases was higher than controls 64 ± 8.0 years versus 56.6 ± 7.6 years respectively. In the multivariate analysis, BMI adjusted OR 0.88 (95% CI: 0.82 – 0.94), menopause adjusted OR 13.33 (95% CI: 1.56 – 113.5), History of fragility fracture adjusted OR 0.07 (95% CI: 0.015 – 0.37) and hypothyroidism adjusted OR 0.31 (95% CI: 0.13 – 0.78) were significantly associated with osteoporosis. BMI, menopause, history of fragility fracture and hypothyroidism were significantly associated with osteoporosis in this study population. Studies with larger sample size and focused exposure should be carried out to draw conclusive relationship with osteoporosis.