Abstract Background Computed tomography perfusion (CTP) of the brain, are increasingly being employed for the assessment of critically ill patients admitted to intensive care units (ICU), including comatose cardiac arrest patients (CCAP). The purpose of our study was to validate the use of CTP in predicting in-hospital mortality in CCAPs. Method This prospective cohort study enrolled newly admitted adult CCAP, with an out of hospital cardiac arrest (OHCA) and were scheduled for admission to the ICU for further management. Just before ICU admission, CCAP underwent a routine CT scan of the head and CTP of whole head. The treating physicians remained blinded to the CTP results and all patients received standard management. The CTP maps were evaluated to determine a binary outcome of non-survivable brain injury (NSBI), by two independent neuroradiologists, blinded to each other’s assessment and to the clinical history of the patients. Results A total of 91 patients were enrolled and 90 (Male-78; mean age-62 years) were included in the final analysis. One patient declined consent. Of these, 42 individuals (47%) had in-hospital mortality. Patients with in-hospital mortality were older; had higher levels of creatinine, blood urea nitrogen, blood CO2 and lower pH, carbonate, and heart rate. In multivariate analysis, PCI was independently associated with reduction in-hospital mortality. CTP demonstrated exceptionally high specificity (100%; 95% CI 92–100%) and positive predictive value (100%; 95%CI 6.3–100%) for the prediction of NSBI. For CTP, Bennet’s S-score showed excellent agreement between the two readers (s = 0.82–0.95). Conclusion CTP was safe and demonstrated very high specificity and positive predictive value and may be used as an additional diagnostic tool for identifying patients at high risk of in-hospital mortality.