The diagnosis of acute pulmonary embolism (PE) remains difficult, and diagnostic strategies must consider the unique challenges of hospitalized and critically ill patients. Diagnostic algorithms that are effective and safe for outpatients may not be effective and safe for inpatients or patients in intensive care units. For example, serial compression ultrasonography (US) of the lower extremities may allow physicians to avoid pulmonary angiography for stable inpatients or outpatients, but this strategy is not validated for patients who require intensive care for serious underlying cardiopulmonary disease. Helical computed tomography (CT) is particularly suited for the evaluation of suspected PE for inpatients with serious cardiopulmonary disease. However, the safety of withholding treatment when a helical CT pulmonary angiogram is negative remains to be demonstrated. Lung perfusion and ventilation scans combined with an assessment of pretest probability remain important objective tests for the evaluation of many hospitalized patients.