BACKGROUND: Pain, dyspnea, and anxiety are common among patients with cancer, heart failure (HF), and chronic obstructive pulmonary disease (COPD), yet little is known about the severity of symptoms over time. OBJECTIVE: To determine the prevalence, severity, burden, and predictors of symptoms during the course of hospitalization and at 2 weeks after discharge. DESIGN: A prospective cohort study. SETTING: A large academic university. PATIENTS: Patients were 65 years or older with a primary diagnosis of cancer, COPD, or HF. MEASUREMENTS: Daily living skills and depression were recorded at enrollment. Symptoms were assessed daily and 2 weeks postdischarge. RESULTS: At baseline, most participants reported moderate/severe pain (54%), dyspnea (53%), and anxiety (62%). Almost two-thirds (64%) had 2 or more symptoms at a moderate/severe level. The prevalence of moderate/severe symptoms decreased at the 24-hour assessment (pain = 42%, dyspnea = 45%, anxiety = 55%, burden = 55%) and again at follow-up (pain = 28%, dyspnea = 27%, anxiety = 25%, burden = 30%). While there was no association between primary diagnosis and symptom severity at baseline or 24-hour assessment, at 2-week follow-up, a higher percentage of patients with COPD had moderate/severe pain (54%, χ2 = 22.0, P = 0.001), dyspnea (45%, χ2 = 9.3, P = 0.05), and overall symptom burden (55%, χ2 = 25.9, P = 0.001) than those with cancer (pain = 22%, dyspnea = 16%, symptom burden = 16%) or HF (pain = 25%, dyspnea = 24%, symptom burden = 28%). Predictors of symptom burden at follow-up were COPD (odds ratio [OR] = 7.5; 95% confidence interval [CI] = 2.0, 27.7) and probable depression (OR = 6.1; 95% CI = 2.1, 17.8). CONCLUSION: The majority of inpatients with chronic illness reported high severity of symptoms. Symptoms improved over time but many patients, particularly those with COPD, had high symptom severity at follow-up. Journal of Hospital Medicine 2012; © 2012 Society of Hospital Medicine