The present study assessed potential associations between vitamin intake and leukemia in a national sample of adults in the United States. A total of 5520 participants were included in this cross-sectional study to investigate the relationship between vitamin intake (including vitamins A, C, D, and E) and leukemia. Results revealed negative associations between vitamin C and E intake and leukemia, whereas associations between vitamin A and D and leukemia were not statistically significant. For vitamin C, compared with the first tertile, the odds ratio (OR) and corresponding 95% confidential interval (CI) was 0.90 (0.75-0.95) for the second tertile and 0.82 (0.61-0.90) for the third tertile (p < 0.01). For vitamin E, compared with the first tertile, the OR and 95% CI was 0.92 (0.80-0.96) for the second tertile and 0.86 (0.71-0.92) for the third tertile (p < 0.01). Furthermore, the inverse relationship between intake of vitamins C and E and leukemia were more evident for individuals ≥60 years of age and those with a body mass index >30 kg/m2. Results of this study provide evidence suggesting that intake of vitamin C and E intake may decrease the prevalence of leukemia; however, further large-scale prospective cohort studies are needed to verify these findings.