BACKGROUND: Left ventricular (LV) ejection fraction (EF) measured by two-dimensional echocardiographic (2DE) imaging is an important correlate of survival. Real-time three-dimensional echocardiographic (3DE) imaging has addressed some of the limitations of 2DE imaging. The aim of this study was to determine whether 3DE imaging is more predictive of outcomes than 2DE imaging. METHODS: A total of 529 patients undergoing LV assessment with 2DE and 3DE imaging in 2003 and 2004 at a tertiary referral cardiac center were studied. Patients had a high frequency of cardiovascular risk factors. Images were gathered over four cardiac cycles using a matrix-array transducer, with measurements performed offline. Follow-up (all-cause mortality or cardiac hospitalization) was obtained over 6.6 ± 3.4 years in 455 of 486 patients with images suitable for measurement (94%). RESULTS: There were 194 events (43%), including 75 deaths (16.4%). Larger LV volumes and lower EF were associated with worse outcomes independent of age, heart failure, or end-stage renal disease. In stepwise Cox regression analyses, the associations of cardiac hospitalization and survival with clinical variables (age, chronic kidney disease, and heart failure) were augmented by 3DE EF and end-systolic volume more than by 2DE parameters. The incremental model χ(2) value with 3DE EF was 14.67 (P < .001), compared with 9.72 (P = .002) for 2DE EF. Similarly, in Cox regression analyses of mortality, the effects of clinical variables (age, advanced renal disease, and heart failure) were augmented more by 3DE EF (incremental χ(2) = 14.04, P < .0001) than 2DE EF (incremental χ(2) = 5.13, P = .024). CONCLUSIONS: In this outcome study, 3DE EF and volumes showed stronger associations with outcomes than those derived from 2DE imaging.