Ultraviolet (UV) radiation exposure is known to be the main cause of non-melanoma skin cancers (NMSCs), and preclinical and early clinical studies have shown the protective effects of nicotinamide against UV-induced DNA damage and the development of precancerous lesions. A Phase III double-blind, randomized, controlled trial reports the safety and efficacy of nicotinamide chemoprevention in 386 patients at high risk of NMSC. After 12 months, compared with placebo, treatment with 500 mg nicotinamide twice daily significantly reduced the rate at which new NMSCs and precancerous lesions developed, with no between-group differences in adverse events. This study thus supports the use of nicotinamide — an inexpensive and widely accessible vitamin supplement — for NMSC chemoprevention in high-risk patients.