BACKGROUND: Cross-sectional studies have indicated impaired neurodevelopment by elevated drinking water manganese concentrations (W-Mn), but potential susceptible exposure windows are unknown. OBJECTIVE: To prospectively evaluate effects of W-Mn, from fetal life to school-age, on children’s cognitive abilities and behavior. METHODS: We assessed cognitive abilities using Wechsler Intelligence Scale for Children (WISC-IV) and behavior using Strengths and Difficulties Questionnaire (SDQ) in 1,265 ten-year-old children in rural Bangladesh. Manganese in drinking water, used during pregnancy and by the children at 5 and 10 years, was measured using inductively coupled plasma mass spectrometry. RESULTS: Median W-Mn was 0.20 mg/L (range 0.001-6.6) during pregnancy and 0.34 mg/L (<0.001-8.7) at 10 years. In multivariable-adjusted linear regression analyses, restricted to children with low arsenic exposure, none of the W-Mn exposures were associated with the children's cognitive abilities. Stratifying by gender (p for interaction in general <0.081) showed that prenatal W-Mn (<3 mg/L) was positively associated with cognitive ability measures in girls, but not in boys. W-Mn at all time-points was associated with increased risk of conduct problems, especially in boys (range 24-43% per mg/L). At the same time, the prenatal W-Mn was associated with a decreased risk of emotional problems (OR: 0.39, 95% CI 0.19, 0.82) in the boys. In girls, W-Mn was mainly associated with low prosocial scores (prenatal W-Mn: OR 1.48, 95% CI 1.06, 1.88). CONCLUSIONS: Elevated prenatal W-Mn exposure was positively associated with cognitive function in girls, while boys appeared unaffected. However, early-life W-Mn exposure appeared to adversely affect children's behavior.