Keloids are common fibroproliferative tumors, and their treatment still represents a dilemma. Intralesional triamcinolone acetonide (TAC) injection is effective, but frequently associated with side effects. Pentoxifyllin (PTX) is a vasodilator, anti-inflammatory, and antifibrotic agent. Its intralesional injection in keloids has not been evaluated yet. Evaluating the efficacy and safety of intralesional PTX versus intralesional TAC and their combination for treatment of keloids. Thirty patients with keloids were divided into three equal groups and treated by intralesional injection of TAC, PTX, or their combination (admixed in 1:1 ratio). Injections were repeated every 3weeks until lesional flattening or for maximum of 5sessions. The evaluation was done using the Vancouver Scar Scale and the Verbal Rating Scale for pain and itching. A significant improvement in VSS was detected in all groups. Significantly better improvements in keloid height, pliability, pain, and itching were detected in the TAC and combination groups than in the PTX group. There was a significantly higher incidence of side effects (atrophy, hypopigmentation, telangiectasia, and precipitation of TAC) in the TAC group than in the combination group, while no side effects were reported in the PTX group. A statistically significant reduction in the number of treatment sessions (required to achieve best results) was detected in patients in the combination group. Intralesional injection of PTX is a potentially helpful, safe, and well-tolerated therapeutic tool for keloids, but with lower efficacy than intralesional TAC when used solely. Combining PTX and TAC produces significantly better results for keloid treatment and lowers the risk of TAC-induced side effects.