Background Radiofrequency segmental thermal ablation (RSTA) has become a commonly used technology for occlusion of incompetent great saphenous veins (GSVs). Midterm results and data on clinical parameters are still lacking. Methods A prospective multicenteral trial monitored 295 RSTA-treated GSVs for 36 months. Clinical control visits included flow and reflux analysis by duplex ultrasound imaging and assessment of clinical parameters according to the CEAP classification and Venous Clinical Severity Score (VCSS). Results A total of 256 of 295 treated GSVs (86.4%) were available for 36 months of follow-up. At 36 months, Kaplan-Meier survival analysis showed the probability of occlusion was 92.6% and the probability of no reflux was 95.7%, and 96.9% of legs remained free of clinically relevant axial reflux. If complete occlusion was present at the 12-month follow-up, the risk of developing new flow by 24 and 36 months of follow-up was 3.7% and 4.1%, respectively. Diameters of the GSV measured 3 cm distal to the saphenofemoral junction reduced from 5.8 ± 2.1 mm at screening to 2.2 ± 1.1 mm at 36 months. The average VCSS score improved from 3.9 ± 2.1 before treatment to 0.9 ± 1.5 at 3 months ( P < .0001) and stayed at an average <1.0 during the complete 36 months of follow-up. Only 41.1% of patients were free of pain before treatment; at 36 months, 251 (98.0%) reported no pain and 245 (95.7%) did not experience pain during the 24 months before. At 36 months, 189 of 255 legs (74.1%) showed an improvement in CEAP class compared with the clinical assessment before treatment ( P < .001). Stages C 3 and C 4 combined to 46% before treatment and dropped constantly to a combined level of 8% at 36 months. However, the proportion of C 2 legs that dropped from 52.3% before treatment to <10% at 12 months showed a constant increase thereafter, reaching 33.3% at 36 months. Conclusion RSTA showed a high and durable success rate in vein ablation in conjunction with sustained clinical efficacy.