Overall survival and recurrence-free survival (RFS) in patients with glioblastoma directly depend on the radicality of tumor resection. According to a number of literature sources, it is known that endoscopic surgeries under fluorescence control increase the rate of total resection. However, until now, there is little data on whether endoscopic resection with fluorescence control affects RFS and overall survival of patients with glioblastoma. The aim of our study was to investigate the effect of intraoperative endoscopic and fluorescence control on overall survival and RFS in patients with glioblastoma. A retrospective single-center analysis was performed in 20 patients with glioblastoma. Ten patients underwent tumor resection using an operating microscope with endoscopic and fluorescence control. In 5 patients, 5-aminolevulinic acid (5-ALA) (alasens) at a dose of 20 mg/ kg was used as a photosensitizer, in 5 patients, chlorin e6 (photoditazine) at a dose of 1 mg/kg. Ten patients underwent resection under endoscopic control, but without fluorescence control. Both cohorts of patients were comparable in age, functional status, tumor localization, adjuvant treatment methods, and molecular status. The criteria for assessing the effectiveness of the study in the groups were: the radicality of the surgical intervention according to postoperative magnetic resonance imaging with contrast enhancement, as well as the median RFS and OS in patients. In the group of combined surgery under microscopic and fluorescence control with an endoscope, the rate of total tumor resection was higher than in the group of patients who underwent only surgery under a microscope and an endoscope without fluorescence control (100% versus 60%; p = 0.002). Median OS (20.2 months (95% CI 11.9-28.6) versus 16.3 months (95% CI 11.0-20.9); (p = 0.003)) and median RFS (11.7 months (95% CI 9.8-15.7) versus 9.8 months (95% CI 6.1-13.4) (p = 0.04)), were also statistically significantly higher compared to the group of patients who received treatment to the same extent, but without fluorescence control. As our experience has shown, the use of fluorescence control during tumor resection in patients with glioblastoma with endoscopic assistance is certainly necessary, given the technical capabilities available, as it has a positive effect on the treatment results for this category of patients.