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Injury to the skin can cause abnormal wound healing and continuous inflammation that leads to the formation of hypertrophic scars and keloids. These lesions often cause significant negative impact on a patient's life due to aesthetic, physical, social, and psychological consequences. Numerous treatment modalities exist for these hypertrophic scars and keloids, which include silicone sheeting, pressure garments, intralesional injection/topical application of scar-modulating agents, laser therapy, and surgical excision. Due to increased efficacy, an evolving treatment paradigm encourages the use of multiple treatment modalities instead of one treatment modality. However, no gold standard treatment exists for these lesions, leaving many people with unsatisfactory results. Adding scar-modulating agents such as 5-Fluorouracil, bleomycin, or Botulinum Toxin A to triamcinolone monotherapy has emerged as a potential drug combination for treating hypertrophic scars and keloids. We sought to critically analyze the evidence that exists for the use of more than one scar-modulating agent. This was done by conducting a systematic review to determine the efficacy of these combined drug regimens. We found that many of these combinations show evidence of increased efficacy and fewer/similar adverse events to triamcinolone monotherapy. Triamcinolone and 5-Fluorouracil showed the strongest and most consistent evidence out of all combinations. With this review, we intend to encourage more research into unique drug combinations that may improve outcomes for patients with symptomatic hypertrophic scars or keloids. [ABSTRACT FROM AUTHOR]