Objective: To compare the safety and efficacy of Varisolve® 1% polidocanol microfoam sclerosant with alternative treatments for patients with varicose veins and trunk vein incompetence. Methods: An open-label, multicentre, prospective trial of 710 patients randomized to receive either Varisolve® or alternative treatment (surgery or sclerotherapy). The endpoint was ultrasound-determined occlusion of trunk vein(s) and elimination of reflux, analysed against a non-inferiority hypothesis. Results: Overall, non-inferiority was demonstrated with 83.4% efficacy for Varisolve® compared with 88.1% for alternative treatment at three months, and the corresponding magnitudes were 78.9 and 80.4% at 12 months. Surgery was superior to Varisolve®, but the success rate of 68.2% for Varisolve® (surgery 87.2%) was poor compared with 93.8% success for Varisolve® achieved in those randomized to Varisolve® or sclerotherapy. Varisolve® was superior to sclerotherapy at 12 months ( P = 0.001). Deep vein thrombosis occurred in 11/437 (2.5%) after Varisolve®, in 1/125 (0.8%) after sclerotherapy and in none after surgery. No pulmonary emboli were detected. Conclusion: Overall, Varisolve® was non-inferior to alternative treatment. Surgery was more efficacious, but Varisolve® caused less pain and patients returned to normal more quickly. The Varisolve® technique is a useful additional treatment for varicose veins and trunk vein incompetence.