The aim of this work was to evaluate the efficacy and safety of intralesional injection of 5-fluorouracil and bleomycin in the treatment of keloids and hypertrophic scars. One hundred and twenty patients were divided into the following groups: group IA was injected intralesionally with 5-fluorouracil; group IB was injected intralesionally with a combination of triamcinolone acetonide and 5-fluorouracil; group II was injected intralesionally with bleomycin. Patients underwent follow up by photographing and Vancouver scar scale system. There was a significant improvement in the Vancouver scar scale in group II compared to group I after treatment. There was hyperpigmentation, pain and ulceration in all the studied groups. Pain was significantly decreased in group IB compared to that in group IA, ulceration was significantly decreased in group II than in group I while pain after injection was increased in group II than in group I. Relapse occurred in 12 patients of group IA, 14 patients of group IB and no relapse occurred in group II. So, intralesional injection of bleomycin was more effective and better in remission than intralesional 5-fluorouracil injection in the treatment of keloids and hypertrophic scars regardless of patient’s age, sex, disease duration or site of the lesion.  2015 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).