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Diarrheal diseases are a leading cause of childhood morbidity and mortality in Latin America. Most studies have focused on infants but not on older children. We enrolled 505 children (age, 12–59 months) with diarrhea and age-matched controls in a case-control study in São Paulo, Brazil. Independent risk factors for diarrhea included another household member with diarrhea (matched odds ratio [mOR], 8.1; attributable fraction [AF], 0.17; P < .001) and consumption of homemade juice (mOR, 1.8; AF, 0.10; P = .01); protective factors included boiling of the baby bottle or nipple (mOR, 0.60; AF, 0.19; P = .026), childcare at home (mOR, 0.58; AF, 0.12; P = .004), and piped sewage (mOR, 0.58; AF, 0.05; P = .047). Hand washing by the caretaker after helping the child defecate protected against Shigella infection (mOR, 0.35; P < .05). Preparation of rice, beans, or soup in the morning and serving it to children after noon were associated with enterotoxigenic Escherichia coli infection (mOR, 8.0; P < .05). In these poor households, 28% of cases of diarrhea in 1–4-year-old children was attributable to easily modifiable exposures.