BACKGROUND. The symptoms of influenza infection in outpatients are well described. The Centers for Disease Control and Prevention (CDC) definition of an influenza-like illness (ILI) includes fever and cough or sore throat. Few data exist on the clinical presentation of influenza in hospitalized patients, which may be distinct from the clinical presentation of influenza in ambulatory patients because of underlying medical conditions and medications. design. Retrospective case-control study. SETTING. A 1,250-bed urban teaching hospital. PATIENTS. A total of 369 patients were admitted to the general medicine wards during 3 consecutive influenza seasons (2001-2004): 123 case patients with laboratory-confirmed influenza that was diagnosed during routine medical care and 246 control patients with active surveillance culture results negative for influenza. METHODS. Data on demographic characteristics, comorbidities, and signs and symptoms were obtained from a review of the medical records of the case and control patients. Analysis included stratified analysis and logistic regression. RESULTS. Cough, coryza, sore throat, and fever were more common in patients with influenza infection. The CDC's definition of an ILI had a sensitivity of 43% and specificity of 86% in the study population, with a crude odds ratio (OR) of 4.7 (95% confidence interval [CI], 2.8-7.8). The sensitivity of the CDC's definition of an ILI decreased to 21% among asthmatic patients, who had similar rates of fever and/or ILI with or without influenza. By logistic regression, ILI was strongly associated with influenza infection in patients without asthma (adjusted OR, 7.5 [95% CI, 4.1-13.7]) but not in patients with asthma (adjusted OR, 1.1 [95% CI, 0.13-10]). The positive predictive value of an ILI in asthmatic patients was 50%. CONCLUSIONS. The CDC's definition of an ILI lacks sensitivity among hospitalized patients, and the presence of an ILI is not associated with influenza infection in asthmatic patients.