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Uncontrolled studies have suggested that vitamin D insufficiency causes diffuse musculoskeletal pain.Comparison of vitamin D levels in patients with diffuse musculoskeletal pain with controls; evaluation of the effect of treatment with vitamin D on diffuse pain.25-Hydroxyvitamin D levels were measured in patients with diffuse musculoskeletal pain and osteoarthritis (controls) recruited from a community rheumatology practice. The diffuse pain patients with 25-hydroxyvitamin D levels ≤20 ng/mL were randomized to receive placebo or ergocalciferol 50,000 IU once weekly for 3 months. Outcomes assessed were pain measured by visual analog scale (VAS) and functional pain score (FPS).One hundred eighty-four patients with diffuse pain and 104 with osteoarthritis entered the study. Mean 25-hydroxyvitamin D levels did not differ between the groups (diffuse pain 29.2 ng/mL ± 13.0, controls 28.8 ng/mL ± 10.5; P = 0.78); nor did the percent of patients in each group with vitamin D levels ≤20 ng/mL (diffuse pain 29%, controls 20%; P = 0.09). Fifty patients with diffuse pain who had 25-hydroxyvitamin D levels ≤20 ng/mL were randomized to receive vitamin D or placebo for 3 months. Vitamin D treatment had no effect on pain in comparison to baseline (VAS P = 0.73; FPS P = 0.18) or at 3 months in comparison to placebo (VAS P = 0.12; FPS P = 0.05, in favor of placebo).Low vitamin D levels are not associated with diffuse musculoskeletal pain, and treatment with vitamin D does not reduce pain in patients with diffuse pain who have low vitamin D levels.