Ulceration of the leg is a major cause of morbidity with venous causes accounting for the majority. Fibroblasts have been incorporated into various tissue-engineered products used for a variety of clinical applications including the treatment of chronic venous leg ulcers.Objectives: The aim of this work was to study the effectiveness of autologous cultured dermal fibroblasts in the treatment of chronic venous leg ulcers.Design: Prospective, comparative, clinical trial.Patients and methods: Forty patients with chronic venous leg ulcers were included in the study. Patients were selected from the vascular surgery outpatient clinic of Kasr Al-Aini University Hospital. The patients included thirty-six males and four females. The patients were divided into two groups (A and B) with 20 patients in each group. Patients in group A were treated with autologous fibroblasts in addition to conventional compression therapy, while patients in group B were treated with conventional compression therapy alone. Clinical follow up was done every week for ten weeks. Statistical evaluation was done at five and ten weeks after starting the therapy.Results: There was no statistically significant difference between group A and B regarding age, sex, duration, site, side of the ulcer, and presence of old DVT, primary varicose veins or incompetent perforators before starting therapy. Also, there was no statistically significant difference between both groups regarding the initial length, width or circumference of the ulcers. Both lines of therapies were effective in reducing the ulcers’ dimensions five and ten weeks after starting the treatment. The percent reductions in the ulcers’ length, width and circumference were statistically more significant in group A compared to group B at five and ten weeks after therapy (P values <0.01⃰). Within each group, none of the age of the patient, duration, side of the ulcer, and presence of incompetent perforators had a statistically significant effect on the percent reduction in the ulcers’ dimensions at five and ten weeks after therapy. Females had a lower response in both groups. The site of the ulcer had no effect on the response to the treatment in group A. On the other hand, ulcers situated on the lateral side or those on the front of the legs had a lower response than ulcers situated on the medial aspect of the legs in group B. Conclusions: Autologous fibroblast therapy is a new therapeutic modality for chronic venous leg ulcers that if combined with compression therapy gives superior results to compression therapy alone.