Objective Refluxing perforators contribute to venous ulceration. We sought to describe patient characteristics and procedural factors that (1) impact rates of incompetent perforator vein (IPV) thrombosis with ultrasound-guided sclerotherapy (UGS) and (2) impact the healing of venous ulcers (CEAP 6) without axial reflux. Methods A retrospective review of UGS of IPV injections from January 2010 to November 2012 identified 73 treated venous ulcers in 62 patients. Patients had no other superficial or axial reflux and were treated with standard wound care and compression. Ultrasound imaging was used to screen for refluxing perforators near ulcer(s). These were injected with sodium tetradecyl sulfate or polidocanol foam and assessed for thrombosis at 2 weeks. Demographic data, comorbidities, treatment details, and outcomes were analyzed. Univariate and multivariable modeling was performed to determine covariates predicting IPV thrombosis and ulcer healing. Results There were 62 patients (55% male; average age, 57.1 years) with active ulcers for an average of 28 months with compression therapy before perforator treatment, and 36% had a history of deep venous thrombosis and 30% had deep venous reflux. At a mean follow-up of 30.2 months, ulcers healed in 32 patients (52%) and did not heal in 30 patients (48%). Ulcers were treated with 189 injections, with an average thrombosis rate of 54%. Of 73 ulcers, 43 ulcers (59%) healed, and 30 (41%) did not heal. The IPV thrombosis rate was 69% in patients whose ulcers healed vs 38% in patients whose ulcers did not heal ( P  < .001). Multivariate models demonstrated male gender ( P  = .03) and warfarin use ( P  = .01) negatively predicted thrombosis of IPVs. A multivariate model for ulcer healing found complete IPV thrombosis was a positive predictor ( P  = .02), whereas a large initial ulcer area was a negative predictor ( P  = .08). Increased age was associated with fewer ulcer recurrences ( P  = .05). Predictors of increased ulcer recurrences were hypertension ( P  = .04) and increased follow-up time ( P  = .02). Calf vein thrombosis occurred after 3% (six of 189) of injections. Conclusions Thrombosis of IPVs with UGS increases venous ulcer healing in a difficult patient population. Complete closure of all IPVs in an ulcerated limb was the only predictor of ulcer healing. Men and patients taking warfarin have decreased rates of IPV thrombosis with UGS.