Recent guidelines have emphasized actively avoiding fever to improve outcomes in patients who are comatose following resuscitation from cardiac arrest (ie, out-of-hospital cardiac arrest). However, whether targeted temperature management between 32 °C and 36 °C (TTM32-36) can improve neurologic outcome in some patients remains debated. Is there an association between the use of TTM32-36 and outcome according to severity assessed at ICU admission using a previously derived risk score? Data prospectively collected in the Sudden Death Expertise Center (SDEC) registry (France) between May 2011 and December 2017 and in the Resuscitation Outcomes Consortium Continuous Chest Compressions (ROC-CCC) trial (United States and Canada) between June 2011 and May 2015 were used for this study. Severity at ICU admission was assessed through a modified version of the Cardiac Arrest Hospital Prognosis (mCAHP) score, divided into tertiles of severity. The study explored associations between TTM32-36 and favorable neurologic status at hospital discharge by using multiple logistic regression as well as in tertiles of severity for each data set. A total of 2,723 patients were analyzed in the SDEC data set and 4,202 patients in the ROC-CCC data set. A favorable neurologic status at hospital discharge occurred in 728 (27%) patients in the French data set and in 1,239 (29%) patients in the North American data set. Among the French data set, TTM32-36 was independently associated with better neurologic outcome in the tertile of patients with low (adjusted OR, 1.63; 95%CI, 1.15-2.30; P= .006) and high (adjusted OR, 1.94; 95%CI, 1.06-3.54; P= .030) severity according to mCAHP at ICU admission. Similar results were observed in the North American data set (adjusted ORs of 1.36 [95%CI, 1.05-1.75; P= .020] and 2.42 [95%CI, 1.38-4.24; P= .002], respectively). No association was observed between TTM32-36 and outcome in the moderate groups of the two data sets. TTM32-36 was significantly associated with a better outcome in patients with low and high severity at ICU admission assessed according to the mCAHP score. Further studies are needed to evaluate individualized temperature control following out-of-hospital cardiac arrest.