Background Compression therapy is considered the gold standard of care for chronic venous disorder and venous leg ulcer treatment. Sclerotherapy is the treatment of choice for reticular varicosities and telangiectasia. Duplex ultrasonography improves the safety and efficacy of conventional sclerotherapy, gives a better evaluation of its results, and provides an understanding of the advantages of using sclerosant in the form of foam. The aim of our study was to compare the results of Duplex-guided foam sclerotherapy for the injection of incompetent perforators versus multiplelayer compression therapy in the treatment of chronic venous ulcer. Patients and methods The present study included 58 patients of chronic venous ulcers. Patients were divided randomly into two equal groups: group I (foam) comprising 29 patients treated by Duplex-guided foam sclerotherapy and group II (compression) comprising 29 patients treated by multiple-layer compression therapy. The statistical analysis was carried out using SPSS. Results There were statistically significant increases in the frequency of perforation among group I, while there was a statistically significant increase in the frequency of incomplete perforation among group II. There was a statistically significant increase in the frequency of complications among group I compared with group II. The most frequent complication was abscess. Conclusion Compared with multiple-layer compression therapy of incompetent perforators to treat venous ulcers, the use of foam injection sclerotherapy of incompetent perforators is feasible and effective, without serious complications and with easy repeated access and ablation of recanalized or new incompetent perforator veins.