Chronic venous insufficiency (CVI) is a progressive disease that is often associated with incompetent perforator veins (IPVs) that exacerbate venous hypertension, ulceration, and reduced quality of life. Minimally invasive techniques such as cyanoacrylate ablation (CA) and radiofrequency ablation (RFA) have become alternatives to traditional surgical methods. However, comparative data on their efficacy and safety remain scarce. We retrospectively analyzed 118 patients with IPVs who underwent either CA (n = 55) or RFA (n = 63) between January 2018 and January 2024. Outcomes included vein closure rates at 1, 3, and 12 months; ulcer healing rates; quality of life (CIVIQ-20 scores); and procedure-related complications. At 12 months, the RFA group demonstrated a significantly higher full closure rate (88.8%) than the CA group (72.7%; P = .044). Ulcer healing rates were similar between groups (85% vs 80%; P = .134), while CIVIQ-20 scores improved significantly in the RFA group (-19.5 +/- 4.5 vs -15.5 +/- 3.5; P = .041). Both techniques exhibited low complication rates with no significant differences in adverse events. CA and RFA are effective and safe options for treating IPVs in patients with advanced CVI. However, RFA demonstrates superior long-term vein closure rates and greater improvements in quality of life, making it the preferred approach in many cases. While CA remains a viable alternative for selected patients, these findings underscore the significance of tailoring treatment strategies to optimize patient outcomes, particularly favoring RFA for its long-term efficacy.