Bartonella bacilliformis has caused debilitating illness since pre-Incan times, but relatively little is known about its epidemiology. A population-based, prospective cohort investigation was conducted in a Peruvian community with endemic bartonellosis. By use of house-to-house and hospital surveillance methods, cohort participants were monitored for evidence of bartonellosis. Of 690 participants, 0.5% had asymptomatic bacteremia at study initiation. After 2 years of follow-up, the incidence of infection was 12.7/100 person-years. The highest rates were in children <5 years old, and there was a linear decrease in incidence with increasing age. Seventy percent of cases were clustered in 18% of households. Age and bartonellosis in a family member were the best predictors of B. bacilliformis infection. There were multiple clinical presentations and significant subclinical infection. A cost-effective control strategy should include vector control and surveillance efforts focused on children and clusters of households with highest endemicity.