Background: Osteoporosis is a common disease characterized by reduction in bone mass, due to depletion of calcium and bone protein. A pivotal role of the sympathetic nervous system in bone remodeling has been considered. On the other hand, elevated central sympathetic activation in postmenopausal women is involved in the creation of vasomotor symptoms. Also, sympathetic skin response (SSR) has been performed for evaluation of the peripheral and central autonomic nervous system dysfunctions. Therefore, to determine the association of the autonomic nervous system and osteoporosis, we evaluated the correlation between the bone mineral density (BMD) with the frequency of vasomotor symptoms and also sympathetic skin responses. Methods: This is a cross-sectional study in which thirty-three postmenopausal osteoporosis women, as the case group, and 31 age-matched postmenopausal women with normal BMD, as the control group, were included in our study. To evaluate the autonomic function, we assessed the frequency of vasomotor symptoms with a questionnaire and performed SSR test for the two groups. According to the parametrical or the nonparametrical distribution of the data, Independent Samples t-test or Mann Whitney test, respectively, were used to compare group differences.Results: The onset latencies of SSR recorded from both hands and feet were significantly prolonged in the case group compared with the control group (P<0.001). Amplitudes of SSR in the case group were significantly less than those of the control group (P<0.001). The postmenopausal osteoporotic women reported a significantly higher frequency of hot flashes and night sweats when compared with non-osteoporotic women (P<0.001).Conclusion: The higher frequency of vasomotor symptoms and impaired sympathetic skin responses in postmenopausal osteoporotic women suggests a role of autonomic dysfunction in osteoporosis.