BACKGROUND AND OBJECTIVES: Rhinoviruses frequently cause respiratory infections in young children. We aimed to establish the burden of acute respiratory infections caused by rhinovirus during the first 2 years of life. METHODS: In this prospective birth cohort study, we followed 923 children for acute respiratory infections from birth to 2 years of age. Data on respiratory infections were collected by daily symptom diaries, study clinic visits, and from electronic registries. Respiratory viruses were detected by reverse transcription-polymerase chain reaction and antigen assays during respiratory infections and at the age of 2, 13, and 24 months. The rates of rhinovirus infections and associated morbidities were determined. RESULTS: We documented 8847 episodes of acute respiratory infections, with an annual rate of 5.9 per child (95% confidence interval [CI], 5.7-6.1). Rhinovirus was detected in 59% of acute respiratory infections analyzed for viruses. Rhinovirus was associated with 50% of acute otitis media episodes, 41% of wheezing illnesses, 49% of antibiotic treatments, and 48% of outpatient office visits for acute respiratory infections. The estimated mean annual rate of rhinovirus infections was 3.5 per child (95% CI, 3.3-3.6), 47 per 100 children (95% CI, 42-52) for rhinovirus-associated acute otitis media, and 61 per 100 children (95% CI, 55-68) for rhinovirus-associated antibiotic treatment. The prevalence of rhinovirus at 2, 13, or 24 months of age was 14 to 24%, and 9% of asymptomatic children were positive for rhinovirus. CONCLUSIONS: Rhinovirus infections impose a major burden of acute respiratory illness and antibiotic use on young children.