Chronic arsenic poisoning remains a public health crisis in Bangladesh. As arsenic has been shown to bind to human hemoglobin (Hb), hematologic mechanisms may play a role in the pathway through which arsenic exerts its toxicity. Two separate studies, a case-control and a cohort, were conducted to investigate the role of Hb in the development of arsenic-induced skin lesions. In the first, conditional logistic regression was used to investigate the effect of Hb on skin lesions among 900 case-control pairs from Pabna, Bangladesh, in which individuals were matched on gender, age, and location. In the second, mixed linear regression models were used to examine the association between toenail arsenic, urinary arsenic, and Hb within a cohort of 184 individuals from 50 families in the same region who did not have arsenic-induced skin lesions. Hb was significantly associated with skin lesions but this association was gender specific. In males, a 40% reduction in the odds of skin lesions occurred for every 1 g/dL increase in Hb (odds ratio, 0.60; 95% confidence interval, 0.49-0.73). No effect was observed for females (odds ratio, 1.16; 95% confidence interval, 0.92-1.46). In the cohort of 184 individuals, no associations between toenail arsenic or urinary arsenic species and Hb levels were observed. Low Hb levels may exacerbate the detrimental health effects of chronic arsenic poisoning. Whereas providing clean water remains the optimal solution to Bangladesh's problem of arsenic poisoning, improving nutrition and reducing iron-deficiency anemia may ameliorate negative health effects, such as skin lesions in individuals who have been exposed.