The authors have previously demonstrated that VenaSeal (Medtronic, Inc, Minneapolis, Minn) adhesive, compared with radiofrequency ablation (RFA, ClosureFast; Medtronic, Inc), in treatment of refluxing saphenous veins in CEAP 6 limbs, results in shorter healing times of venous ulcers. The authors hypothesize that the longer treated length possible with VenaSeal's nonthermal modality may affect the number of critical refluxing perforators contributing to the nonhealing wound. This follow-up study compares the need for follow-up treatment of perforator veins after saphenous vein treatment with either radiofrequency ablation (ClosureFast RFA) or adhesive closure (VenaSeal). A multi-institutional retrospective review of CEAP 6 patients who had closure of their saphenous veins from 2015 to 2020 was conducted. Patients who underwent follow-up treatment of perforator veins were grouped according to their method of initial management of their saphenous veins. The primary end point was incidence of a perforator procedure after ClosureFast or VenaSeal ablation. Secondary end points included sclerotherapy to facilitate wound healing. Bivariate analysis used the χ2 test, Fisher exact test, t-test, and Wilcoxon rank sum test. A P value of <.05 defined statistical significance. There were 119 CEAP 6 patients with saphenous closure: 51 limbs treated with VenaSeal and 68 with RFA. Median follow-up was 105 days (interquartile range: 44, 208). All limbs achieved wound healing during the study period. Mean time to wound healing post index procedure was shorter for VenaSeal than RFA (72 vs 293.8 days, P > .0009), as was median time (43 vs 104 days, P = .001). More limbs treated with RFA had previous known deep vein thrombosis (29% vs 10%, P = .009), deep venous insufficiency (82% vs 51%, P = .0003), and perforator reflux (57% vs 29%, P = .002). Limbs with identified follow-up perforator reflux treated with RFA had a higher prevalence of initially treated saphenous veins with RFA compared with those treated with VenaSeal (49% vs 27%, P = .003). There was no difference between the methods of vein closure and use of concurrent sclerotherapy. ClosureFast and VenaSeal are both effective and safe modalities of saphenous ablation, but VenaSeal treatment was associated with less perforator RFA intervention.