Vitamin C functions as a regulator of the catabolism of cholesterol to bile acids in the guinea pig and has been demonstrated to be an important factor in lipid regulation of the guinea pig, rabbit and rat. Correlation studies in humans have shown an inverse relationship between vitamin C intake and cardiovascular disease mortality. Observational and experimental studies in humans have yielded inconsistent results, but taken together indicate that for individuals with high total cholesterol concentrations,≥5.20 mmol/L (200 mg/dl) and less than full tissue saturation, increasing the concentration of vitamin C may have a salutary effect on total cholesterol. Vitamin C’s effect on promoting the production and inhibiting the degradation of prostacyclin is reviewed, as are implications of these findings regarding thrombosis and atherogenesis. Evidence indicative of a protective effect on lipid peroxidation by vitamin C is examined. Analysis of the literature regarding groups at high risk for coronary heart disease reveals that men, the elderly, smokers, diabetics, hypertensives and perhaps oral estrogen-containing contraceptive users have lowered plasma vitamin C levels. Evidence linking vitamin C to human cardiovascular disease is largely circumstantial, but taken in total, is suggestive of an association. Further examination of the relationship between vitamin C and cardiovascular disease is warranted.