Keloids characterize a definitely challenging type of cutaneous scars for which a diversity of therapeutic modalities has been suggested. The aim of this work was to compare the therapeutic efficacy of intralesional injection of botulinum toxin type‐A (BTX‐A), platelet rich plasma (PRP), and triamcinolone acetonide (TAC) in keloids. A total of 60 keloids patients were enrolled and divided randomly into three equal groups. Group I treated by intralesional BTX‐A injection, group II treated by intralesional PRP injection, and group III treated by intralesional TAC injection. Clinical assessment was done by Vancouver Scar Scale (VSS), Verbal Rating Scale (VRS), and dermoscopic examination. Additionally, histopathology and immunohistochemistry of connective tissue growth factor (CTGF) expression were evaluated. The results of this study revealed significant improvement of both VSS and VRS in response to all treatment modalities. There was significant improvement of VSS in BTX‐A and PRP groups more than TAC group. However, no significant difference observed between BTX‐A and PRP groups. Immunohistochemical examination showed significant decrease of CTGF expression after treatment in BTX‐A and PRP groups more than TAC group. In conclusion, both BTX‐A and PRP could yield a chance for cosmetically better outcomes in keloids treatment than conventional TAC injection.