OBJECTIVE: In observational studies, low vitamin D levels are associated with type 2 diabetes (T2D), impaired glucose metabolism, insulin sensitivity, and insulin secretion. We evaluated the efficacy of vitamin D supplementation on insulin sensitivity and insulin secretion in subjects with T2D and low vitamin D (25-hydroxyvitamin D [25(OH)D] <50 nmol/L). RESEARCH DESIGN AND METHODS: Sixty-two men and women with T2D and vitamin D deficiency participated in a 6-month randomized, double-blind, placebo-controlled trial. Participants received a single dose of 400,000 IU oral vitamin D or placebo, and the vitamin D group received an additional 200,000 IU D if serum 25(OH)D was <100 nmol/L after 4 weeks. Primary end points were total by euglycemic clamp with assessment of endogenous glucose production and first-phase insulin secretion by intravenous glucose tolerance test. RESULTS: In the vitamin D group, the mean ± SD baseline serum 25(OH)D of 38.0 ± 12.6 nmol/L increased to 96.9 ± 18.3 nmol/L after 4 weeks, 73.2 ± 13.7 nmol/L after 3 months, and 53.7 ± 9.2 nmol/L after 6 months. The total exposure to 25(OH)D during 6 months (area under the curve) was 1,870 ± 192 and 1,090 ± 377 nmol/L per week in the vitamin D and placebo groups, respectively ( < 0.001). Insulin sensitivity, endogenous glucose production, and glycemic control did not differ between or within groups after treatment ( = 0.52). First-phase insulin secretion did not change significantly after treatment ( = 0.10). CONCLUSIONS: Replenishment with a large dose of vitamin D to patients with T2D and vitamin D deficiency did not change insulin sensitivity or insulin secretion. These findings do not support such use of therapeutic vitamin D supplementation to improve glucose homeostasis in patients with T2D.