RATIONALE: Lung cancer is the leading cause of cancer-related mortality in the United States. Although supplements are used by half the population, limited information is available about their specific effect on lung cancer risk. OBJECTIVES: To explore the association of supplemental multivitamins, vitamin C, vitamin E, and folate with incident lung cancer. METHODS: Prospective cohort of 77,721 men and women aged 50-76 years from Washington State in the VITAL (VITamins And Lifestyle) study. Cases were identified through the Seattle-Puget Sound SEER (Surveillance, Epidemiology, and End Results) cancer registry. MEASUREMENTS AND MAIN RESULTS: Hazard ratios (HRs) for incident lung cancer according to 10-year average daily use of supplemental multivitamins, vitamin C, vitamin E, and folate. A total of 521 cases of lung cancer were identified. Adjusting for smoking, age, and sex, there was no inverse association with any supplement. Supplemental vitamin E was associated with a small increased risk of lung cancer (HR, 1.05 for every 100-mg/d increase in dose; 95% confidence interval [CI], 1.00-1.09; P = 0.033). This risk of supplemental vitamin E was largely confined to current smokers (HR, 1.11 for every 100-mg/d increase; 95% CI, 1.03-1.19; P < 0.01) and was greatest for non-small cell lung cancer (HR, 1.07 for every 100-mg/d increase; 95% CI, 1.02-1.12; P = 0.004). CONCLUSIONS: Supplemental multivitamins, vitamin C, vitamin E, and folate were not associated with a decreased risk of lung cancer. Supplemental vitamin E was associated with a small increased risk. Patients should be counseled against using these supplements to prevent lung cancer.