BACKGROUND: Resection of left hemisphere (LH) tumors is often complicated by the risks of causing language dysfunction. Although neurosurgeons' concerns when operating on the presumed dominant hemisphere are well known, literature evaluating laterality as a predictive surgical parameter in glioblastoma (GB) patients is sparse. We evaluated whether tumor laterality correlated with surgical performance, functional outcome, and survival, METHODS: AU patients with GB treated at our institution between 2006 and 2016 were reviewed. Analysis comprised clinical characteristics, extent of resection (EOR), neurologic outcome, and survival in relation to tumor lateralization. RESULTS: Two hundred thirty-five patients were included. Right hemisphere (RH) tumors were larger and more frequently extended into the frontal lobe. Preoperatively, limb paresis was more frequent in RH, whereas language deficits were more frequent in LH tumors (P = 0.0009 and P < 0.0001, respectively). At 6 months after resection, LH patients presented Lower Karnofsky Performance Status (KPS) score (P 0.036). More patients with LH tumors experienced dysphasia (P < 0.0001), and no difference was seen for paresis. Average FOR was comparable, but complete resection wag achieved less often in LH tumors (37.7 vs. 64.8%; P = 0.0028). Although overall survival did not differ between groups, progression-free survival was shorter in LH tumors (7.4 vs. 10.1 months; P = 0.0225). CONCLUSIONS: Patients with LH tumors had a pronounced KPS score decline and shorter progression-free survival without effects on overall survival. This observation might partially be attributed to a more conservative surgical resection. Further investigation is needed to assess whether systematic use of awake surgery and intraoperative mapping results in increased FOR and improved quality survival of patients with GB.