Background and objectives: In the Indian subcontinent, psoriasis cases have skyrocketed in the last decade. Dry and hot weather aggrandizes the annual incidences. Nowadays, dermatologists harness methotrexate and apremilast to manage chronic plaque psoriasis. There needs to be more comparative studies on these drugs. The primary objective was change in Psoriasis Area and Severity Index (PASI) at six months from the baseline. Change in Dermatology Life Quality Index (DLQI) at six months from the baseline and incidences of adverse events served as the secondary objectives.Methods: This randomized, open-label, 24-week study was executed in Srirama Chandra Bhanja (SCB) Medical College, Cuttack, India, from June 2021 to October 2022. The participants were randomized in a 1:1 ratio to receive tablets of either methotrexate 10-15mg weekly once or apremilast 10-30mg twice daily. Efficacy and safety analyses were performed at baseline, eight, 16, and 24 weeks. We used R software (version 4.1.1; R Foundation for Statistical Computing, Vienna, Austria) for data analysis.Results: Seventy (82.3%) of 85 enrolled participants completed the study. The mean age of the study population was 41.08±5.17 years. Twenty-two (31.4%) of them were females. The median change in PASI from baseline was -37.25 (-39.00 to -34.25) for apremilast and -34.75 (-37.75 to -31.75) for methotrexate (p=0.006). The median change in DLQI from baseline was -19.50 (-22.00 to -17.00) for apremilast and -21.00 (-25.50 to -17.50) for methotrexate (p=0.079). No serious adverse events were noticed.Conclusion: Apremilast was more effective than methotrexate in psoriasis treatment. The statistically significant difference was found only in PASI scores.