Pain is a common complaint among postmenopausal women. It has been postulated that vascular dysfunction caused by estrogen decline at menopause plays a key role in the initiation and progression of degradative joint disease, namely age-related osteoarthritis. We evaluated whether supplementation with resveratrol, a phytoestrogen, could improve aspects of well-being such as chronic pain that is commonly experienced by postmenopausal women.A 14-week randomized, double-blind, placebo-controlled intervention with trans-resveratrol (75 mg, twice daily) was conducted in 80 healthy postmenopausal women. Aspects of well-being, including pain, menopausal symptoms, sleep quality, depressive symptoms, mood states, and quality of life were assessed by Short form-36 at baseline and at the end of treatment. Rating scales were averaged to provide a composite score representing overall well-being. Cerebral vasodilator responsiveness to hypercapnia was also assessed as a surrogate marker for cerebrovascular function.Compared with placebo treatment, there was a significant reduction in pain and an improvement in total well-being after resveratrol supplementation. Both benefits, including measures of quality of life, correlated with improvements in cerebrovascular function.Our preliminary findings indicate potential for resveratrol treatment to reduce chronic pain in age-related osteoarthritis. Resveratrol consumption may also boost perceptions of well-being in postmenopausal women. Further investigation to elucidate underlying mechanisms is warranted.