Abstract Background Seizures are the most common & most serious side effect of cranial surgery. The latter condition requires chronic treatment with Antiepileptic drugs (AEDs) and comes with relevant socioeconomic sequelae. The routine prophylactic use of AEDs for people undergoing tumor resection has remained controversial due to the risk of postoperative seizures. Some Neurosurgeons are advocates to the use of AEDs to reduce the risk of these seizures. Objective To evaluate the efficacy of prophylactic AEDs routinely in brain tumor patients without previous history of seizures. Primary objective has been to identify the efficacy of AEDs in perioperative seizure prophylaxis. Secondary objective has been to highlight the most common type of post-operative AEDs. Methods All available studies from 2000-2021 including randomized or non-randomized clinical trials, prospective or retrospective observational cohort studies, and case series of six or more cases that address these criteria have been collected. Results Our search concluded that the most common type of post-operative seizure is the Early seizure which is of total 87 patients representing 12.3% of seizure reported patients, yet when comparing the P-value between the Early & late seizure it has a P-value of 0.415 which is nonsignificant rendering the comparison redundant. The Most common types of AED used are Phenytoin (PHT) 89 (71.8%) & Levetiracetam (LEV) 109 (81.8%). To measure the efficacy of AEDs two groups of patients with no history of AED administration or seizures preoperatively were created, one the control group of 268 participants were not administered AEDs postoperatively only 32 (11.94%) of them suffered from seizures postoperatively. The other group of 171 participants were administered the AEDs postoperatively only 25 (14.62%) of these participants suffered from postoperative seizure. Comparing both of these results statistically it had a P-value of 0.416 which is non-Significant statistically. On interpreting these results was that the AED have no influence in controlling the seizures. Conclusion Postoperative seizures are one of the main complications of brain tumor surgery. Neurosurgeons have a strong belief more of tradition that preventing seizures with Anti-Epileptic Drugs (AEDs) as a sort of seizure prophylaxis is not only effective but also necessary. Finally, there is not enough evidence of sufficient quality available to suggest that antiepileptic drugs AEDs treatment can or cannot be recommended to reduce Post-craniotomy seizures.