The aims of this study were (1) to evaluate the prognostic value of negative wall motion (WM) and myocardial perfusion during contrast-dobutamine stress echocardiography (DSE), (2) to determine whether WM-myocardial contrast echocardiography (MCE) had incremental prognostic value over just WM during DSE in patients with chest pain in the emergency room (ER), and (3) to compare the prognostic value of negative DSE-WM, and DSE-WM-MCE to nuclear-myocardial perfusion imaging (N-MPI) in a similar patient population over the same time period. We retrospectively studied 569 patients with real time contrast DSE, and 147 patients underwent N-MPI for evaluation of chest pain. Follow-up for cardiac events was obtained between 12 and 25 months. The cumulative cardiac event-free survival was 94.5% in negative DSE-WM, 97.1% in negative DSE-WM-MCE and 96.7% in negative N-MPI group. Cardiac event-free survival of the negative DSE-WM-MCE group was significantly higher than the DSE-WM group (log rank P < 0.01), and similar in the DSE-WM-MCE group compared to the N-MPI group. Combined WM and perfusion during DSE was the strongest independent predictor for cardiac events. The negative predictive power of DSE-WM-MCE is superior to that of just negative DSE-WM and is comparable to that of N-MPI. Myocardial perfusion and WM analysis during DSE provide independent information for predicting cardiac events in patients with chest pain syndrome in the ER.