Background: Respiratory syncytial virus (RSV) is the most common cause of severe respiratory illness in infants. To help direct targeted interventions and future RSV vaccine programs, we examined risk of RSV-related hospitalization by infant age and birth month. Methods: We conducted Poisson regression analyses to evaluate birth month as a risk factor for RSV-related pediatric hospitalizations (identified by any mention of ICD-9-CM diagnosis codes: 466.11, 480.1 or 079.6) from State Inpatient Data in Arizona, Iowa, New York, Oregon and Wisconsin between July 1996 and June 2006. We used an age cohort approach to compute total relative risk of RSV during the first year of life. Results: We identified 82,296 RSV-related infant hospital admissions, corresponding to 13.9 per 1000 person-years among infants <12 months of age. Of these, 42% of the patients were female and 73% were <6 months old. One-month-old infants born in January were ~10 times more at risk for RSV-related hospitalization than 1-month-old infants born in October [relative risk: 9.8 (7.8–12.4)]. Across the first year of life, infants born in December and January had a 2- and 3-fold higher risk, respectively, of an RSV-related hospitalization event than infants born in July. Conclusions: Birth month and age at admission impacted the risk of RSV-related hospitalization within the first year of life in 5 states we investigated. As RSV vaccine candidates are currently under investigation in clinical trials, our findings help identify ideal RSV vaccine schedules to prevent early and severe events while improving the use of expensive prophylactic drugs.