BACKGROUND:: Few community studies have measured the incidence, severity and etiology of acute respiratory illness (ARI) among children living at high-altitude in remote rural settings. METHODS:: We conducted active, household-based ARI surveillance among children aged <3 years in rural highland communities of San Marcos, Cajamarca, Peru from May 2009 through September 2011 (RESPIRA-PERU study). ARI (defined by fever or cough) were considered lower respiratory tract infections if tachypnea, wheezing, grunting, stridor or retractions were present. Nasal swabs collected during ARI episodes were tested for respiratory viruses by real-time, reverse-transcriptase polymerase chain reaction. ARI incidence was calculated using Poisson regression. RESULTS:: During 755.1 child-years of observation among 892 children in 58 communities, 4475 ARI were observed, yielding an adjusted incidence of 6.2 ARI/child-year (95% confidence interval: 5.9-6.5). Families sought medical care for 24% of ARI, 4% were classified as lower respiratory tract infections and 1% led to hospitalization. Of 5 deaths among cohort children, 2 were attributed to ARI. One or more respiratory viruses were detected in 67% of 3957 samples collected. Virus-specific incidence rates per 100 child-years were: rhinovirus, 236; adenovirus, 73; parainfluenza virus, 46; influenza, 37; respiratory syncytial virus, 30 and human metapneumovirus, 17. Respiratory syncytial virus, metapneumovirus and parainfluenza virus 1-3 comprised a disproportionate share of lower respiratory tract infections compared with other etiologies. CONCLUSIONS:: In this high-altitude rural setting with low-population density, ARI in young children were common, frequently severe and associated with a number of different respiratory viruses. Effective strategies for prevention and control of these infections are needed. © 2014 Lippincott Williams and Wilkins.