BACKGROUND: Children under five bear the largest cholera burden. We therefore sought to identify modifiable risk factors among Bangladeshi children. METHODOLOGY/PRINCIPAL FINDINGS: We used multivariate Poisson regression to assess risk factors for severe cholera among diarrheal patients presenting at hospitals in Matlab (rural) and Dhaka (urban), Bangladesh. Risk increased with age. Compared to those under one, rural and urban four-year-olds had adjusted risk ratios (aRR) of 4.17 (95% confidence interval (CI) 2.43-7.15) and 6.32 (95% CI: 4.63-8.63), respectively. Breastfeeding halved the risk in both rural (aRR = 0.49, 95% CI: 0.35-0.67) and urban (aRR = 0.51, 95% CI: 0.41-0.62) settings. Rural children's risk decreased with maternal education (P-trend: <0.001) and increased among those with a family member with diarrhea in the past week (aRR = 1.61, 95% CI: 1.22-2.14) and those with prior vitamin A supplementation (aRR = 1.65, 95% CI: 1.12-2.43). Urban children whose mothers daily (aRR = 0.41, 95% CI: 0.21-0.79) or occasionally (aRR = 0.55, 95% CI: 0.36-0.84) read a newspaper experienced reduced risk. Urban children from households with incomes between 34-84 USD/month had a 30% increased risk compared to those from households with incomes >84 USD/month. CONCLUSION/SIGNIFICANCE: Increasing age, lower socioeconomic status, and lack of breastfeeding are key correlates of increased risk for cholera hospitalization among those under five in rural and urban Bangladesh. In addition, having a family member with diarrhea in the past week was associated with increased risk among rural children. Continued attention should be directed to the promotion of breastfeeding. Further research is needed to elucidate the relationship between maternal education and cholera risk. Renewed research regarding the use of chemoprophylaxis among family members of cholera cases may be warranted in rural endemic settings.