Low 25-hydroxyvitamin D status has been associated with a higher risk of cancer in epidemiologic studies. The aim of this study was to undertake a systematic review and meta-analysis of randomized clinical trials (RCTs) investigating the effect of vitamin D supplementation alone on cancer incidence and mortality. A systematic review was undertaken. MEDLINE, Embase, CENTRAL, conference abstracts, and clinical trial registries were searched (last search March 2017) for RCTs investigating vitamin D supplementation alone. RCTs with ≥12 mo of follow-up and in participants with a mean or median age ≥60 y were eligible. During-study events were used as the main analysis, but after-study events were included in a secondary analysis. Subgroup analyses concerning different forms of vitamin D supplementation, 25-hydroxyvitamin D status at baseline, vitamin D dose, and exclusion of open-label trials were undertaken. Thirty studies in 18,808 participants were included in the systematic review, with a median follow-up ranging from 1 to 6.2 y. The results of the meta-analysis for during-study events showed no evidence of an effect of vitamin D supplementation for cancer incidence (RR: 1.03; 95% CI: 0.91, 1.15) and cancer-related deaths (RR: 0.88; 95% CI: 0.70, 1.09). Including after-study events, the RRs were 1.02 (95% CI: 0.92, 1.13) and 0.86 (95% CI: 0.72, 1.03), respectively. These results did not appear to be affected by baseline 25-hydroxyvitamin D status, vitamin D dose, or the exclusion of open-label trials. We did not find evidence to suggest that vitamin D supplementation alone reduces the incidence of cancer or cancer mortality, even after including long-term follow-up results.