OBJECTIVE: This study was designed to analyze the results of recurrent glioblastoma (GBM) treatment, investigate the changes in molecular expression on paired primary and recurrent tumor specimens of GBM, and evaluate the effect of these changes on patient survival. METHODS: A total of 170 adult patients were diagnosed with recurrent GBM at a single institution between 2005 and 2015. Patients were divided into the reoperation and nonoperation groups. In addition, we evaluated the expression of immunologic markers of 43 paired surgical specimens from the first and second operations. RESULTS: The median overall survival (OS) after recurrence in the reoperation group was significantly longer than that in the nonoperation group (median, 9.1 months vs. 5.6 months; P = 0.024). The groups differed in characteristics such as age, performance scale, and progression-free survival. In the reoperation group, higher performance scale at recurrence, better extent of resection, and adjuvant treatment were related to longer overall survival. Among 43 paired surgical specimens, programmed death-ligand 1 (PD-L1) was positively expressed in 17 (39.5%) and 6 (13.9%) patients after the first and second operations, respectively. PD-L1 expression after recurrence showed an increase, decrease, and no change in 6 (13.9%), 14 (32.5%), and 23 (53.4%) patients, respectively. Changes in PD-L1 expression after recurrence did not affect survival after recurrence during progression. CONCLUSIONS: The extent of resection and adjuvant treatment was important for prolonged survival. Reoperation without adjuvant treatment was not effective for prolonged survival. Initial and follow-up PD-L1 expression from both operations did not influence patient survival.