Massive thrombotic intraoperative pulmonary emboli (IOPE) is rare but carries a great degree of morbidity and mortality. This is the first study to formally assess the utility of various tools for the diagnosis of these events and the impact of each tool on mortality. Due to both the infrequent occurrence of these events and the high mortality of massive IOPE, it was cost-prohibitive to prospectively randomize patients to study commonly used diagnostic tools. Hence, a descriptive review of all reported cases in the literature was performed. This review yielded 146 cases for past 4 decades. Following a careful review of these cases, the alerting monitor for the occurrence of IOPE was recorded. Furthermore, we recorded the confirming diagnostic tool and the outcome of these patients. We compared 4 monitoring tools: (1) end-tidal carbon dioxide; (2) central catheter pressures; (3) echocardiography; and (4) standard monitoring of vital signs. Pre-event use of transesophageal echocardiography had no survival benefit. End-tidal carbon dioxide changes as an alerting tool were associated with improved survival compared to changes in vital signs (P<0.0001). Signs of right heart strain were associated with greater mortality, but direct thrombus visualization was not. Echocardiography appears to be useful for diagnosis of massive IOPE. Compared with hemodynamic collapse, end-tidal carbon dioxide decline as the presenting sign of massive IOPE may be associated with a better prognosis because it may represent earlier detection of IOPE and allow for more time to intervene.