ABSTRACT Objective Electrical cortical stimulation (ECS) has been the gold standard for intraoperative functional mapping in neurosurgery, yet it carries the risk of induced seizures. Here we assess the safety of focal cortical cooling (CC) as a potential alternative to ECS for functional brain mapping. Methods We retrospectively reviewed 40 consecutive subjects (n=13 tumor, 27 mesial temporal lobe epilepsy (MTLE) resection) who underwent intraoperative CC during craniotomy at the University of Iowa Hospital and Clinics from 2007 through 2019 (CC group). Thirty-eight of the 40 subjects had ECS performed along with CC during the same procedure. To assess the safety of CC, intra- and post-operative seizure incidence and post-operative neurological deficits were collected together with new post-operative radiographic findings not related to the surgical procedure itself (i.e. non-mapping portions). As a control cohort, we collected 55 consecutive subjects (n=21 MTLE, 34 tumor/vascular pathology) who underwent awake ECS mapping without CC between 2006 and 2019 (ECS-alone group). To evaluate potential long term effects of mapping techniques (CC and/or ECS), we separately collected another 25 consecutive subjects who underwent anterior temporal lobectomy(ATL) without CC nor ECS between 2007 and 2019 (No ECS/No CC-ATL group). Results A total of 79 brain sites were cooled in the 40 CC subjects, including inferior frontal gyrus (44%), precentral gyrus (39%), postcentral gyrus (6%), subcentral gyrus (4%) and superior temporal gyrus (6%). No intraoperative seizures were reported in the CC group, whereas 3.6% of ECS-alone group had intraoperative seizures. The incidence of seizure(s) within the first post-operative week did not significantly differ amongst CC (7.9%), ECS-alone (9.0%) and No ECS/No CC-ATL groups (12%). There was no significante difference in the incidence of postoperative radiographic change between CC (7.5%) and ECS-alone groups (5.5 %). The long term seizure outcome for MTLE subjects did not statistically differ regarding ‘good’ outcomes (Engel I+II): CC group (80%), ECS-alone (83.3%) and No ECS/No CC-ATL group (83.3%). Conclusions Cortical cooling when used as an intraoperative mapping technique is safe, and may complement traditional electrical cortical stimulation.