9016 Background: Vitamin D has pleiotropic effects, which may moderate the interaction between patients and their tumors. Two studies were carried out to test the hypothesis that higher vitamin D levels reduce the risk of relapse from melanoma. Methods: A pilot retrospective case-control study in 271 melanoma patients suggested that vitamin D may protect against recurrence of melanoma. We then tested these findings in a survival analysis in a cohort of 872 cases recruited to the Leeds Melanoma Cohort (median follow up of 4.7 years). Results: Pilot study Results suggested that taking vitamin D reduced the risk of relapse from melanoma (OR 0.6, 95% CI: 0.4, 1.1). Non-relapsers had higher mean 25-dihydroxyvitamin D3 levels than relapsers (49 nmol/L compared with 46, p=0.3). Cohort study Higher 25-dihydroxyvitamin D3 levels were associated with lower Breslow thickness at diagnosis and were independently protective of relapse and death: hazard ratio (HR) for relapse free survival (RFS) 0.76, 95% CI: (0.64, 0.96), for a 20nmol/L increase in serum level. There was evidence of interaction between the vitamin D receptor (VDR) BsmI genotype and serum 25-dihydroxyvitamin D3 levels on RFS. Conclusions: The pilot study provided preliminary evidence for a role for vitamin D in outcome from melanoma. The cohort study provided further evidence that higher 25-dihydroxyvitamin D3 levels, at diagnosis, were associated both with thinner tumors and better survival, independent of Breslow thickness, from melanoma. Melanoma patients should avoid vitamin D deficiency. Further studies are needed to establish optimal serum levels for melanoma patients. No significant financial relationships to disclose.