Elevated C-reactive protein levels are associated with the risk of cardiovascular disease and diabetes. We examined whether multivitamins reduce C-reactive protein levels.We performed a post hoc subgroup analysis of a 6-month, randomized, double-blind, placebo-controlled trial. Patients (n = 87; mean age, 53 years) for whom frozen plasma samples were available; who did not have an inflammatory condition at baseline; and who were not hospitalized, taking antibiotics, smoking, or starting statin therapy during the study were included. C-reactive protein and plasma vitamin levels were measured at baseline and 6 months.At 6 months, C-reactive protein levels were significantly lower in the multivitamin group than in the placebo group (between-group difference = -0.91 mg/L; 95% confidence interval: -1.52 to -0.30; P= 0.005). The reduction in C-reactive protein levels was most evident in patients who had elevated levels (>/=1.0 mg/L) at baseline. Of the six vitamins measured (C, E, B(6), B(12), folate, and beta carotene), only vitamin B(6) (baseline: r = -0.31, P= 0.003; 6 months: r = -0.29, P= 0.006) and vitamin C (baseline: r = -0.25, P= 0.02) were inversely associated with C-reactive protein level.In a post hoc analysis of a randomized, double-blind, placebo-controlled study, multivitamin use was associated with lower C-reactive protein levels. Other similarly formulated multivitamins may yield comparable results.