Background: Patients with IDH-mutant 1p/19q-codeleted grade 3 oligodendroglioma (O3^IDHmt/Codel) benefit from adding alkylating chemotherapy to radiotherapy (RT). However, the optimal chemotherapy regimen between Procarbazine, CCNU, and Vincristine (PCV) and Temozolomide (TMZ) remains unclear given the lack of randomized trial data comparing both regimens. Methods: The objective was to assess the overall (OS) and progression-free (PFS) survival associated with first-line PCV/RT versus TMZ/RT in patients diagnosed with O3^IDHmt/Codel. We included patients with histologically-proven O3^IDHmt/Codel (according to WHO criteria) from the French national prospective cohort study POLA. All tumours underwent central pathological review. OS and PFS from surgery were estimated using Kaplan-Meier method and Cox regression model. Results: 305 newly-diagnosed O3^IDHmt/Codel patients treated with RT and chemotherapy between 2008 and 2022 were included. 67.9% of patients (n=207) were treated with PCV/RT and 32.1% with TMZ/RT (n=98). Median follow-up was 78.4 months (IQR=44.3-102.7). Median OS was not reached (95%CI: NR-NR) and 140 months (95%CI: 110-NR) in the PCV/RT and TMZ/RT groups, respectively (log-rank P<0.0001). On univariable analysis, there was a significant difference in favor of PCV/RT in both 5-year (PCV/RT: 89%, 95%CI: 85-94; TMZ/RT: 75%, 95%CI: 66-84) and 10-year OS (PCV/RT: 72%, 95%CI: 61-85; TMZ/RT: 60%, 95%CI: 49-73), which was confirmed in the multivariable Cox model adjusted for age, type of surgery, gender, ECOG performance status and CDKN2A homozygous deletion (HR 0.53 for PCV/RT, 95%CI: 0.30-0.92, P=0.025). Conclusions: In patients with newly-diagnosed O3^IDHmt/Codel from the POLA cohort, first line PCV/RT was associated with better OS outcomes compared to TMZ/RT. Our data suggest that the improved safety profile associated with TMZ comes at the cost of inferior efficacy in this population. Further investigation using prospective randomized studies is warranted.