The effectiveness of epilepsy surgery is mostly based on the results of observational studies because an experimental design in surgical patients has several ethical implications. However, observational studies suffer from methodological drawbacks, which prevent meaningful conclusions and represent a serious limitation when data from different reports are pooled for systematic reviews and meta-analyses. These include the retrospective design, the use of referral populations, the small sample size, the enrolment of patients at differing inception points, the use of differing inclusion criteria, differing definitions of prognostic predictors and outcome measures, the unmasked assessment of outcome, the short follow-up, the changing technologies and surgical procedures, and the inadequate statistical methods. With these limitations in mind, a systematic review was performed of epilepsy surgery studies aiming at identifying the positive and negative prognostic predictors of surgical outcome. In this review, extent of surgical resection, abnormal MRI, mesial temporal sclerosis, febrile seizures, EEG/MRI concordance, and tumor were in decreasing order the principal indicators of the success of surgery of epilepsy. By contrast, intracranial monitoring and post-operative discharges tended to predict an unfavorable prognosis. Although the heterogeneity of the study results was fairly low, the results may be affected by pooling of data from heterogeneous reports (different patient series assessed with differing methods) or unexamined or unknown confounders. These data must be considered preliminary and cannot replace well-conducted prognostic studies (representative study populations, well-defined inception cohorts, satisfactory and complete follow-up, prospective design, and standard definition of prognostic factors).