OBJECTIVE: To determine factors that affect caregivers’ decisions about antibiotic use in children in settings where antibiotics are available without prescription. METHODS: In a house-to-house survey, 1200 caregivers in 3 periurban districts of Lima, Peru, were asked about antibiotic use in young children. RESULTS: In this sample, 87.2% of children aged <5 years had received an antibiotic drug in their lives; 70.3% had received antibiotics before 1 year of age, and 98.8% of those had been prescribed by a physician. Given hypothetical cases of common cold and nondysenteric diarrhea, caregivers would seek medical advice in 76.4% and 87.1%, respectively, and 84.6% of caregivers said they respected medical decisions even if an antibiotic was not prescribed. Caregivers with high school–level education accepted 80% more medical decisions of not using an antibiotic and used fewer pharmacist-recommended antibiotics. For each additional year of life, the risk of self-medicated antibiotic use and the use of pharmacist-recommended antibiotics increased in 30%. (OR: 1.3, 95% CI: 1.1–1.4, P = .001 and OR: 1.3, 95% CI: 1.2–1.5, P < .001, respectively). Caregivers respected a medical decision of not prescribing an antibiotic 5 times more when physicians had explained the reason for their advice (OR: 5.0, 95% CI: 3.2–7.8, P < .001). CONCLUSIONS: Prescribed antibiotic use in these young children is common. Even if they are available without prescription, caregivers usually comply with medical advice and follow physicians’ recommendations when antibiotics are not prescribed. Improving physician prescribing habits could reduce irrational antibiotic use, decreasing future caregiver-driven misuse.