Background Limited data exist regarding the epidemiology and prognosis of seizures in adults after cardiac surgery. The aim of this study was to define preoperative predictors of seizures and impact on postoperative outcomes. Methods A prospective database of 2,578 consecutive adults who underwent cardiac surgery at a single institution between April 2007 and December 2009 was retrospectively analyzed to determine risk factors for postoperative seizures and prognostic impact. No patient received tranexamic acid or aprotinin. Results Seizures occurred in 31 patients (1%) at a median of 2 days postoperatively (1 patient had a preoperative diagnosis of seizure disorder). Seizures were classified as generalized tonic-clonic (71%), simple/complex partial (26%), or status epilepticus (3%). Incidence differed according to procedure (coronary bypass 0.1%, isolated valve 1%, valve/coronary bypass 3%, aorta 5%; p <0.001). Patients who experienced seizures had nearly a fivefold higher operative mortality than patients who did not (29% versus 6%, p <0.001). Head computed tomography was performed in 26 patients (84%), of whom ischemic strokes were identified in 14 cases (53%). These were embolic in 9 patients (34%), and watershed in 3 (12%). Hemorrhagic strokes were observed in 2 patients (8%). The occurrence of a new postoperative stroke in seizure patients did not significantly increase the likelihood of in-hospital death. Thirteen patients (41%) were discharged without neurologic deficit. Multivariable logistic regression analysis identified three risk factors for seizure: deep hypothermic circulatory arrest, aortic calcification or atheroma, and critical preoperative state. Conclusions Seizures in adults after cardiac surgery are strong independent predictors of permanent neurologic deficit and increased operative mortality. Early head computed tomography may be indicated to identify treatable pathology.