Objectives The main objective of this prospective study was to clarify the therapeutic efficacy and tolerance of duplex-guided polidocanol foam injection in the treatment of lowflow venous malformations (LFVM), residual symptomatic hemangiomas after medical treatment, and Klippel-Trenaunay syndrome (KTS) performed at Vascular Surgery Department at Zagazig University Hospitals. Patients and methods This prospective study included 36 patients divided into three groups: 17 cases with LFVM, 11 cases with vascular tumors (hemangiomas), and eight cases with KTS. All cases were treated by duplex-guided polidocanol foam sclerotherapy. Results The study included 20 (56%) males. The mean age of the patients was 15.19 years. The final outcome was good response regarding the decrease in size and symptoms in 13 cases of LFVM, six cases of hemangiomas, and six cases of KTS. The remaining four cases of LFVM, five cases of hemangiomas, and two cases of KTS had fair or poor results after sclerotherapy (unfavorable outcome), for which surgical excision was done. There was no statistically significant difference among the three different types of patients regarding outcome or occurrence of complications. Conclusion Duplex-guided polidocanol foam sclerotherapy is easy to perform and is a safe procedure that provides excellent outcome for venous malformations and good outcome for infantile hemangiomas and KTS.