Background Respiratory syncytial virus (RSV) is an established cause of serious lower respiratory disease in children, but the burden in adults is less well studied. Methods We conducted a retrospective study of hospitalizations among adults ?20 years from the 1997-2012 National Inpatient Sample (NIS). Trends in RSV admissions were described relative to unspecified viral pneumonia admissions. Hospitalization severity indicators were compared among immunocompromised RSV, non-immunocompromised RSV, and influenza admissions. Results An estimated 28,237 adult RSV hospitalizations occurred, compared to 652,818 influenza hospitalizations; 34% were immunocompromised individuals. RSV and influenza patients had similar age, gender and race distributions, but RSV was more often diagnosed in urban teaching hospitals (73.0% for RSV vs. 34.6% for influenza) and large hospitals (71.9% vs. 56.4%). RSV hospitalization rates increased from 1997-2012, particularly for those ≥ 60, increasing from 0.5 to 4.6 per 100,000, while unspecified pneumonia admission rates decreased significantly (p<0.001). Immunocompromised patients with RSV hospitalization had significantly higher inpatient mortality (p=0.013), use of mechanical ventilation (p=0.016), mean length of stay (LOS) (p<0.001), and mean cost p<0.001) than non-immunocompromised RSV hospitalizations. Overall, RSV hospitalizations were more severe than influenza hospitalizations (6.2% mortality for RSV vs. 3.0% for influenza, 16.7% vs. 7.2% mechanical ventilation, mean LOS of 6.0 vs. 3.6 days, and mean cost of $38,828 vs. $14,519). Conclusions RSV hospitalizations in adults are increasing, likely due to increasing recognition and diagnosis. The burden of RSV in adults deserves attention. Although there are fewer hospitalizations than influenza, those that are diagnosed are on average more severe.