Psoriasis is a papulosquamous disorder that causes significant social and psychological trauma to the patient. It is characterized by the presence of erythematous, indurated plaques covered with silvery-white scales. Despite the availability of several systemic agents that have been approved for the treatment of psoriasis, usually there are some residual lesions and there is a need to treat them for cosmetic reasons or symptomatic control. 1. Treatment of resistant localized psoriatic plaques or residuals after systemic treatment. 2. Recently, some intralesional agents have been used successfully for the treatment of psoriatic plaques as 5-FU, methotrexate, and botulinum toxin type-A, and nearly for four decades, no study focused on the effect of intralesional corticosteroids in the treatment of these psoriatic plaques. We decided to highlight their role and compare intralesional Triamcinolone to intralesional 5-FU regarding efficacy and safety in the treatment of plaque psoriasis. This study included 24 patients with localized plaque psoriasis. Each patient was treated by split-body therapy where one psoriatic plaque was treated with intralesional 5FU and another plaque with intralesional TAC. A total of three injections were given at 2-week intervals and follow up was regularly every 2 weeks up to 12 weeks. There was a statistically significant difference between both groups (p = 0.008) as the response rate on 5-FU side was 12.5% with no response, 29.2% with a moderate response, 41.7% with an excellent response, and 16.7% with a complete clearance, while on the TAC side it was16.7% with a moderate response, 20.8% with an excellent response and 62.5% with a complete clearance. Hyperpigmentation was the most irritating side effect of 5-FU that occurred. Pain, during and after injection, was greater in 5-FU group. Hypopigmentation and atrophy only occurred in TAC group in some patients but it seems to be reversible and not disfiguring. 1-Intralesional TAC injection may have more efficacy and less side effects than 5-FU injection in the treatment of localized plaque psoriasis. Hyperpigmentation and pain were the most irritating side effects of 5-FU 2-Intralesional TAC can be effective in the treatment of localized psoriatic plaques with minimal side effects, especially in patients not suitable for systemic agents.