It is often difficult to predict outcome in hospitalized patients with pericardial effusion. To address this issue, the prognostic value of echocardiography was studied in 187 hospitalized patients diagnosed with pericardial effusions over a 1-year period. The index echocardiogram showed that 11 effusions were large (6%), 39 were moderate (21%), and 137 were small (73%). Right ventricular collapse was present in 7% of cases (13 of 178), right atrial collapse in 12% (21 of 168), and inferior vena cava (IVC) plethora with blunted response to respiration in 35% (46 of 132). During the course of hospitalization, 9 patients (5%) had cardiac tamponade and 16 (9%) had cardiac tamponade, pericardiocentesis and/or surgical drainage (combined end point). By univariate analysis, each echocardiographic sign was associated with both cardiac tamponade and the combined end point (p less than or equal to 0.01 for comparisons with size and right-sided chamber collapse; p less than or equal to 0.07 for comparisons with IVC plethora). When the data were analyzed with logistic regression modeling, effusion size was the most powerful predictor of outcome (cardiac tamponade: odds ratio 51, 95% confidence interval 3.5-729, p = 0.004; combined end point: odds ratio 78, 95% confidence interval 14-421, p = 0.0001), and neither right-sided chamber collapse nor IVC plethora with blunted response to respiration retained significant associations. It is concluded that echocardiographically determined effusion size is a powerful predictor of outcome in hospitalized patients with pericardial effusion, and that right-sided chamber collapse and IVC plethora with blunted response to respiration add little if any additional prognostic information.