OBJECTIVES:   Due to serious cardiopulmonary reactions reported immediately following administration of perflutren containing contrast agents , the United States Food and Drug Administration (FDA) required a Black Box Safety warning for this class of agents including Perflutren Protein-Type A Microspheres Injectable Suspension , USP.  The FDA has requested a database analysis to compare in-hospital mortality in critically ill patients undergoing echocardiography with and without this contrast agent.  This study provides results of the retrospective analysis.  METHODS:   This study utilized the largest hospital service-level database in the US.  All adult patients undergoing inpatient echocardiography between January 2003 and October 2005 were identified (n=2 ,588 ,722 of which 22 ,499 received Perflutren Protein-Type A Microspheres Injectable Suspension, USP).  From the 22 ,499 contrast echocardiography patients, 2,900 had diagnoses meeting criteria for critical illness (heart failure, acute myocardial infarction, arrhythmia, respiratory failure, pulmonary embolism, emphysema , and pulmonary hypertension).  To control for the differences between the contrast and non-contrast patients we used propensity score matching.  Variables used in the construction of the propensity score included comorbidities , demographic factors , hospital-specific factors , level of care, and mechanical ventilation status.  Patients receiving contrast echocardiography were matched to 4 controls who received non-contrast echocardiography.  Conditional logistic regression was used to estimate mortality effects.  RESULTS:   There were 167 deaths in the study among critically ill patients, 38/2900 from the contrast group and 129/11600 from the control group. The contrast agent was not associated with an increase in same-day mortality (odds ratio = 1.18 (95% C.I. 0.82, 1.71); P= 0.37)). Prior to matching, contrast patients showed greater morbidity then non-contrast patients (Deyo-Charlson Comorbidity Score 2.45 vs. 2.25, P<0.0001). After propensity-score matching these differences were significantly reduced, showing that both groups were well-balanced. CONCLUSIONS:   There is no increase in mortality in critically ill patients undergoing echocardiography with the contrast agent compared to case-matched controls.