BACKGROUND Keloids are benign skin lesions that arise from an abnormal scar formation. It has a worldwide distribution but more in the African population. The areas of predilection include the earlobes, chin, shoulder, and anterior chest. The possible causes of keloid include genetics, trauma, and skin tension. The pathogenesis of keloids is still unknown, which is reflected by the plethora of treatment modalities available to treat keloids. These modalities include excision, injection of triamcinolone, and mechanical compression. The use of an antineoplastic agent as a treatment modality for keloids is because it is evident that keloids are in a hypermetabolic state, and 5-fluorouracil has proven to be an effective treatment. OBJECTIVE This study aims to determine and compare the outcomes of keloidal scar treatment following a combination therapy that includes intralesional excision of keloid and administration of intralesional injections of either triamcinolone or a combination of triamcinolone and 5-fluorouracil. METHOD This work was a prospective, comparative and interventional study carried out at National Orthopaedic Hospital Igbobi and Lagos State University Teaching Hospital Lagos. The study duration was 14 months, and the calculated sample size was 60. The patients were randomly sampled into two equal groups of 30. Group A consisted of patients that had a combination of intralesional excision and triamcinolone. In contrast, Group B consisted of patients that had a combination of intralesional excision with a combination of triamcinolone and 5-fluorouracil. The outcome measures were a comparison of keloid scar characteristics following treatments and the local side effects of the injections. After intralesional excision of the keloid, the outcome measures were observed and measured on weeks 2, 4,6,8,10,12, and 6 weeks after the last dose of injections DATA ANALYSIS The data were analyzed with Statistical Package for Social Sciences (SPSS) version 22 for Windows (SPSS Inc. Chicago, IL), and results were expressed in cross-tabulations, bar charts, and line graph RESULT: Most patients were in the age group of 28-37years with a female gender predominance. Patients that had injections of triamcinolone and 5FU achieved a better percentage reduction of mean keloidal height at the end of the study. Keloidal scar ulceration and pain during the administration of injections were more associated with patients with the regimen containing 5FU. The mean VAS for patients with triamcinolone alone was 2±0.46, while VAS for patients with triamcinolone and 5FU was 8±3.68. None of the patients that had triamcinolone alone had keloidal scar ulceration, while 64.29% of patients that had triamcinolone and 5FU had keloidal scar ulceration.