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Even today methotrexate (MTX) remains the backbone of psoriasis management in dermatological practice. The widespread usage as well as over the counter availability of drug in India has led to frequent incidents of overdosing, resulting in toxicity. However, there is a lack of large size, comprehensive study in literature emphasizing upon reasons behind drug toxicity, clinical manifestations, and various management aspects.The present study aims to evaluate risk factors, clinical features, and suggest best management protocol based upon our experience in the management of MTX toxicity.A multicentric, retrospective study was conducted including all cases of psoriasis who were treated for MTX toxicity in the last 5 years. Complete information including demographic details, drug history, detailed clinical evaluation, laboratory parameters, management protocol, and outcome were studied and analyzed. A total of 21 patients of psoriasis with MTX toxicity were included, of which 20 had mucocutaneous ulcerations and hematological abnormalities were found in 76% patients. All cases were treated with folinic acid and 85% patients recovered within 7-14 days. Three out of 21 patients succumbed to their illness despite the best possible treatment. Overdosing was found to be the most common cause (66%) of drug toxicity, either inadvertent or due to self-medication. Patients must be counseled regarding course of the disease, drug regimen, and dreaded side effects prior to initiating the drug. In case the symptoms of toxicity appear, a prompt medical advice must be sought.