Abstract Background: Vitamin D has many anti-cancer properties such as reducing angiogenesis, inflammation, and cell proliferation, and enhancing apoptosis and cellular differentiation. Epidemiological studies are inconsistent across cancer sites, showing inverse, positive, and null associations with 25-hydroxyvitamin D [25(OH)D] blood concentrations (i.e., the accepted biomarker of vitamin D status). We previously reported that higher 25(OH)D status was related to improved prostate cancer survival, yet few other studies have examined pre-diagnostic vitamin D concentrations and survival after a cancer diagnosis. Methods: Based on measured prospective circulating 25(OH)D from several case-control sets nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish men, we examined serum 25(OH)D (DiaSorin LIAISON 25(OH)D TOTAL assay) in relation to overall and site-specific cancer survival among 3,740 men and 1,946 cancer deaths occurring through December, 2013. Multivariate-adjusted proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between 25(OH)D and survival from malignant melanoma, non-Hodgkin lymphoma, and cancers of the colorectum, lung, prostate, kidney, stomach, oropharynx, larynx, bladder, esophagus, liver, and pancreas. Results: Baseline serum 25(OH)D concentrations were significantly higher among men who were alive at the end of follow-up compared with men who died from their cancer (medians 35.0 vs. 32.1 nmol/L, respectively; p = 0.003). Higher baseline 25(OH)D was associated with lower overall cancer death (HR = 0.75, 95% CI 0.65-0.87 for highest vs. lowest quintile, p-trend 0.0001). Excluding the prostate cancer cases did not materially alter this association (HR = 0.79, 95% CI 0.67-0.82 for highest vs. lowest quintile, p-trend 0.006). Organ site-specific survival showed higher 25(OH)D to be associated with lower risk of death from the following cancers: prostate (Q5 vs. Q1 HR = 0.74, 95% CI 0.53-1.03), renal (Q5 vs. Q1 HR = 0.58, 95% CI 0.32-1.04), stomach (Q5 vs. Q1 HR = 0.49, 95% CI 0.30-0.82), oropharynx/larynx (Q5 vs. Q1 HR = 0.55, 95% CI 0.28-1.06), and melanoma (T3 vs. T1 HR = 0.41, 95% CI 0.18-0.94), and higher risk of death from esophageal cancer (higher vs. below median HR = 1.80, 95% CI 1.04-3.12). Conclusion: Higher pre-diagnostic serum 25(OH)D concentrations were associated with improved overall cancer survival, as well as improved survival for prostate, renal, stomach, oropharyngeal and laryngeal cancers and malignant melanoma, but poorer esophageal cancer survival. The apparent paradox of higher vitamin D status being associated with improved survival, but not necessarily reduced incidence, of these particular cancers deserves further study in other prospective populations. Citation Format: Stephanie J. Weinstein, Alison Mondul, Demetrius Albanes. Association between pre-diagnostic circulating 25-hydroxyvitamin D and cancer survival. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3416.