Introduction: Epileptiform activity is common after cardiac arrest due to the hypoxic-ischemic lesion, resulting in increased morbidity (persistent coma states), and even mortality. Current guidelines for the treatment of status epilepticus after cardiac arrest encompass targeted temperature treatment and the use of antiepileptic drugs. Antiepileptic drugs may be used as primary prevention or treatment for patients with epileptiform activity. However, the exact protocol for the initiation of these drugs or the clinical outcome associated with seizure prophylaxis is not well understood or described. Therefore, this meta-analysis aims to analyze the role of antiepileptic drugs in reducing mortality and improving clinical outcomes in patients after cardiac arrest. Methods: Databases (PubMed, Scopus, and Cochrane) were systematically searched for studies directly comparing antiepileptics with standard care vs. standard care alone for comatose patients after cardiac arrest. Primary outcomes were all-cause mortality, Cerebral Performance Category (CPC), and electroencephalogram (EEG). Results: Four studies comprising 643 comatose patients who survived a cardiac arrest were included. In the pooled data, it was found no difference in cerebral performance (OR 0.69; 95%CI 0.43,1.13; P>0.05) or mortality (OR 1.38; 95%CI 0.51, 3.71; P< 0.0001) between the standard treatment and the intervention with antiepileptic drugs. Heterogeneity for mortality was considerably high (I2= 86%) mostly because of one study which shows a different design concerning the control and intervention groups. Regarding the EEGs, we were unable to do a statistical analysis because the studies used different parameters to evaluate EEGs, although all came to the same conclusion that AEDs improve status epilepticus momentarily but do not ameliorate neurological outcomes long-term. Conclusions: The use of antiepileptics for comatose patients after a cardiac arrest does not improve neurologic outcomes or mortality. There were many limiting factors to the comparison, including multiple drugs used and unstandardized protocol for EEG evaluation. However, the conclusion of the meta-analysis confirms the results of individual trials, showing no benefit in the usage of seizure prophylaxis in this population.