The recommended dietary allowance (RDA) of vitamin C has traditionally been based on the prevention of the vitamin C deficiency disease, scurvy. While higher intakes of vitamin C may exert additional health benefits, the limited Phase III randomized placebo-controlled trials (RCTs) of vitamin C supplementation have not found consistent benefit with respect to chronic disease prevention. To date, this has precluded upward adjustments of the current RDA. Here we argue that Phase III RCTs-designed principally to test the safety and efficacy of pharmaceutical drugs-are ill suited to assess the health benefits of essential nutrients; and the currently available scientific evidence is sufficient to determine the optimum intake of vitamin C in humans. This evidence establishes biological plausibility and mechanisms of action for vitamin C in the primary prevention of coronary heart disease, stroke, and cancer; and is buttressed by consistent data from prospective cohort studies based on blood analysis or dietary intake and well-designed Phase II RCTs. These RCTs show that vitamin C supplementation lowers hypertension, endothelial dysfunction, chronic inflammation, and Helicobacter pylori infection, which are independent risk factors of cardiovascular diseases and certain cancers. Furthermore, vitamin C acts as a biological antioxidant that can lower elevated levels of oxidative stress, which also may contribute to chronic disease prevention. Based on the combined evidence from human metabolic, pharmacokinetic, and observational studies and Phase II RCTs, we conclude that 200 mg per day is the optimum dietary intake of vitamin C for the majority of the adult population to maximize the vitamin's potential health benefits with the least risk of inadequacy or adverse health effects.