Risk factors associated with respiratory failure during respiratory syncytial virus (RSV) infection have not been assessed in adults. We identified RSV by quantitative reverse transcription polymerase chain reaction in 58 adults during the 2007-2008 winter. Clinical variables and respiratory secretion viral loads were compared in 26 outpatients and 32 inpatients. Cardiopulmonary diseases were more common among inpatients than outpatients (91% vs 31%, P = .0001), whereas mean RSV load was similar. Nasal viral load was higher in ventilated vs nonventilated hospitalized patients (log(10) 3.7 +/- 1.7 plaque-forming units (PFUs)/mL vs 2.4 +/- 1.1 PFUs/mL, P = .02), and high viral load was independently associated with respiratory failure.