We prospectively quantified disease severity associated with epidemiologic and socioeconomic parameters as well as the clinical factors in 195 previously healthy infants with confirmed respiratory syncytial virus (RSV) infection. Infants were enrolled into three subgroups according to disease severity: outpatients (82 patients), inpatients (100 patients), and intensive care unit patients (13 patients). Epidemiologic parameters such as gestational age, birth weight, chronologic age at presentation, and gender as well as socioeconomic factors such as ethnic origin, family history of asthma, exposure to cigarette smoke, number of family members, presence of pets at home, breast-feeding, and day-care attendance were not found to predict the severity of RSV illness in previously healthy infants. Our results emphasize the complexity of predicting disease severity in previously healthy infants with RSV infection and suggest that other parameters such as host genetic background might explain the clinical variability.