OBJECTIVES: Due to cost reaching $10,000/season, respiratory syncytial virus (RSV) immunoprophylaxis is limited to high-risk periods, but season determination is heavily debated and absolute risk varies significantly by geographic location. We present monthly RSV incidence rates to estimate absolute burden of disease and numbers needed to treat (NNT) to provide an alternative to a dichotomous season definition. METHODS: Medicaid fee-for service recipients <2 years old from California and Florida (1999-2004) were selected if they met high-risk criteria for RSV infections (chronic lung disease or congenital heart disease based on ICD-9 codes, or prematurity up to 32 weeks’ gestational age based on birth certificates). Monthly RSV hospitalization rates were broken down by recipients’ age and adjusted for the effects of immunoprophylaxis. NNTs were calculated as inverse of the absolute risk reduction (based on relative risk reduction from clinical trial data: 50%). Results in Florida were separated in 5 surveillance regions. RESULTS: California showed a very distinct season from December – March with almost zero viral activity outside. NNTs were smallest in February (<50) but increased with increasing age. In Florida, no months had zero activity; however, NNTs were never below 125, regardless of age. Among children >1 year, the lowest NNT was 252 [95% CI: 129-5,875] and NNTs exceeded 500 for 8 months (January – August). While the northern regions showed a short, distinct season, the southern regions experienced prolonged activity, most obvious in the southeast. Yet, April through July in the southwest and May/June in the southeast showed NNTs exceeding 650 while the winter months had a peak activity that was comparable to other regions. CONCLUSIONS: NNTs can address differences in burden of disease during the RSV season and between geographic regions and assure equitable access to prophylaxis. Reduced RSV incidence in the second year of life should be incorporated in decisions for immunoprophylaxis.