Objective: Thermal ablative techniques of varicose veins carry a risk of heat-related complications, including postoperative pain. Mechanochemical endovenous ablation (MOCA) might avoid these complications and reduce postoperative pain because of the absence of thermal energy. This study evaluated postoperative pain and quality of life after radiofrequency ablation (RFA) and MOCA for great saphenous vein (GSV) incompetence. Methods: Sixty-eight patients with unilateral GSV incompetence were treated with either RFA or MOCA in this prospective observational study. Patients monitored their pain for the first 14 postoperative days on a 100-mm visual analog scale (VAS). They also completed the general (RAND 36-Item Short-Form Health Survey) and disease-specific (Aberdeen Varicose Vein Questionnaire) quality of life questionnaires before and 6 weeks after treatment. Results: Patients treated with MOCA reported significantly less postoperative pain than patients treated with RFA during the first 14 days after treatment (4.8 ± 9.7 mm vs 18.6 ± 17.0 mm; P <.001) (mean VAS over 14 days). The lower postoperative pain score was associated with a significantly earlier return to normal activities (1.2 ± 1.8 vs 2.4 ± 2.8 days; P =.02) and work resumption (3.3 ± 4.7 vs 5.6 ± 5.8 days, respectively; P =.02). At 6 weeks, patients in both groups perceived an improved change in health status and an improved disease-specific quality of life. Conclusions: MOCA is associated with significantly less postoperative pain, faster recovery, and earlier work resumption compared with RFA in the treatment of GSV incompetence. MOCA and RFA are both related to a rapid improvement in quality of life.