Abstract Objective. Ecological studies conducted in the United States and globally have shown an inverse association between levels of solar ultraviolet irradiance and kidney cancer incidence, suggesting that vitamin D, which is obtained from exposure to ultraviolet light (sunlight), may be associated with a reduced risk of kidney cancer. However, results from two prospective cohort and two case-control studies focusing on dietary vitamin D reported no statistically significant association with the development of kidney cancer. Thus, the purpose of this study was to examine the association between circulating 25-hydroxyvitamin D (25(OH)D), the accepted biomarker for vitamin D status, and the development of kidney cancer within a large pooled nested case-control study carried out as part of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP). Methods. Kidney cancer cases (n = 775) and age-, sex-, race-, and season-matched controls (n = 775) were identified from eight prospective cohort studies participating in the VDPP. Data on potential confounders were obtained and harmonized by a central data coordinating center. Serum/plasma samples were assayed for 25(OH)D at Heartland Assays, Inc using the DiaSorin LIAISON 25(OH)D TOTAL assay, a direct, competitive chemiluminescence immunoassay. Clinically-defined cutpoints suggesting deficient, insufficient, and sufficient 25(OH)D concentrations were used to analyze the association between high and low circulating 25(OH)D and kidney cancer, with 50 to <75nmol/L chosen as the reference category. The main analyses were conducted using conditional logistic regression models adjusting for matching variables and potential confounders such as high blood pressure and body mass index. Results. Neither low nor high concentrations of circulating 25(OH)D were significantly associated with kidney cancer risk overall or the renal cell carcinoma subtype. Sex-specific analyses showed, however, that high concentrations of 25(OH)D (>75 nmol/l) were associated with a non-significant increased risk of kidney cancer among males (reference: 50 to <75 nmol/l) (OR=1.52, 95% CI: 0.95, 2.41) and a statistically significant decreased risk among females (OR=0.31, 95% CI: 0.12, 0.85) (interaction P-value = 0.42). Conclusions. The findings from this consortium-based study indicate that vitamin D is not associated with the risk of kidney cancer or the renal cell carcinoma subtype, although additional investigation of the possible modification of the association by sex is warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2800.