Abstract BACKGROUND No standard treatment is validated at first progression in high-risk low-grade gliomas, thus the optimal salvage therapy at recurrence and the factors that influence the PFS and OS are being investigated. MATERIAL AND METHODS We evaluated 71 patients with grade II glioma (WHO 2016) who progressed following surgery and initial chemotherapy with TMZ. Thirty-two (45.1%) patients were oligodendrogliomas IDH 1/2 mutated and 1p19q codeleted, 11 (15.5%) were diffuse astrocytomas IDH mutant, and 28 (39.4%) were diffuse astrocytomas IDH wild-type. Median follow up was 144 months (range 23–180). RESULTS Thirty-one patients (43.7%) underwent second surgery, 24 (33.8%) second-line chemotherapy, and 16 (22.5%) radiotherapy with a median PFS of 58 months (IC 95% 49–116). Median PFS was 60 months after second surgery (IC95% 43–116) and chemotherapy (IC95% 51–69), and 38 months after radiotherapy (IC95% 15–64) (p 0.09). No significant benefit in PFS was achieved in oligodendrogliomas undergoing second surgery (60 months) as compared with oligodendrogliomas treated with radiation or chemotherapy (58 months, p 0.11). PFS of astrocytomas IDH wild-type following second surgery (53 months) did not differ from those patients treated with adjuvant treatments (65 months, p 0.28). Median OS from the first salvage therapy was 117 months (IC95% 93 – 123+): 120 months (IC95% 108–140+) after second surgery, 94 months (IC95% 75–117+) after chemotherapy, and 62 months (IC95% 27–112) after radiotherapy (p 0.04). Median OS (123 months, IC95% 106–154) was prolonged in oligodendrogliomas receiving second surgery as compared to those receiving radiotherapy or chemotherapy (93 months, IC 95% 61–112, p 0.07), while median OS in astrocytomas IDH wild-type did not differ between those who received second surgery or radiotherapy or chemotherapy. CONCLUSION Reoperation as first salvage treatment in grade II gliomas seems to offer a probability of a longer OS, and this could hold true especially for oligodendrogliomas.