Background: Psoriasis is a systemic immune-mediated disease accompanied by arthritis in a significant percentage of patients called psoriatic arthritis. The present study was conducted to compare methotrexate and acitretin in cases of psoriasis. Materials & Methods: 80 patients of palmoplantar psoriasis of both genderswere divided into 2 groups of 40 each. Group I patients were given oral acitretin 0.5mg/kg daily for 3 months and group II were given oral methotrexate15mg/week for 3 months. Modified psoriasis area severity index (MPASI)score was recorded. Improvement was graded as: no change, slight improvement, moderate, marked and almost cleared. Results: There were 15 males and 25 females in group I and 20 males and 20 females in group II. The mean MASI score at baseline, 1 month, 2 months and 3 months was in group I was 61.2, 41.4, 31.2 and 21.6 and in group II was 58.4, 39.2, 24.5 and 15.4. The difference was significant (P< 0.05). Conclusion: Both oral methotrexate and acitretin were highly effective in treating palmoplantar psoriasis. The reduction of Psoriasis lesions with Oral methotrexate was faster than acitretin.