BACKGROUND: Human rhinovirus (HRV) infections are highly prevalent, genetically diverse, and associated with both mild upper respiratory tract and more severe lower tract illnesses (LRTI). OBJECTIVE: To characterize the molecular epidemiology of HRV infections in young children seeking acute medical care. STUDY DESIGN: Nasal swabs collected from symptomatic children <3 years of age receiving care in the Emergency and Urgent Care Departments at Seattle Children\'s Hospital were analyzed by a rapid polymerase chain reaction (PCR) system (FilmArray((R))) for multiple viruses including HRV/enterovirus. HRV-positive results were confirmed by laboratory-developed real-time reverse transcription PCR (LD-PCR). Clinical data were collected by chart review. A subset of samples was selected for sequencing using the 5\' noncoding region. Associations between LRTI and HRV species and genotypes were estimated using logistic regression analysis. RESULTS: Of 595 samples with HRV/enterovirus detected by FilmArray, 474 (80%) were confirmed as HRV by LD-PCR. 211 (96%) of 218 selected samples were sequenced; HRV species A, B, and C were identified in 133 (63%), 6 (3%), and 72 (34%), respectively. LRTI was more common in HRV-C than HRV-A illness episodes (adjusted OR [95% CI] 2.35[1.03-5.35). Specific HRV-A and HRV-C genotypes detected in multiple patients were associated with a greater proportion of LRTI episodes. In 18 patients with >1 HRV-positive illness episodes, a distinct genotype was detected in each. CONCLUSION: Diverse HRV genotypes circulated among symptomatic children during the study period. We found an association between HRV-C infections and LRTI in this patient population and evidence of association between specific HRV genotypes and LRTI.