Background: Dermatologists are using antineoplastic agent methotrexate for more than six decades for various skin diseases. Methotrexate is a dihydrofolate reductase inhibitor and has cytotoxic, anti-inflammatory and steroid sparing effect. However, long term use of methotrexate raises a concern about its safety. Careful monitoring of patients on methotrexate therapy can either minimize or prevent the adverse effects.The aim of the study was to evaluate the adverse drug reactions caused by methotrexate therapy in the treatment of dermotological diseases.Methods: Observational clinical study done in 56 patients with skin diseases, who were on methotrexate therapy. LFT, RFT, blood counts done at baseline and every 2 weeks till the end of six months. Adverse reactions were monitored and assessed using WHO-UMC scale.Results: Among sixteen Psoriasis patients on methotrexate (max 15 mg/wk) therapy, 62.5% experienced adverse effects and the most common ADR being GI upset in 6 patients. Other common adverse effects observed were elevated liver enzymes, leucopenia, thrombocytopenia, candidiasis and elevated serum creatinine. None of the patients in our study had pulmonary toxicity, life threatening adverse effects requiring hospitalisation or secondary lymphoma. Adverse effects caused by methotrexate were dose dependent. So low dose weekly methotrexate regimen with folate supplementation in the form of folic acid or folinic acid can minimize the adverse effects. Conclusions: Our study was successful in identifying the adverse effects caused by methotrexate when used for various skin diseases in the department of dermatology.