Background: Methotrexate (MTX) is used as an anti-cancer drug in higher doses. However, lower doses of methotrexate have been used in the treatment of rheumatic diseases due to its immunosuppressant effects such as rheumatoid arthritis, psoriatic arthritis, inflammatory myopathies, asthma, and other inflammatory conditions. Objective: The current study aimed to estimate the prevalence and severity of methotrexate toxicity among patients receiving low-dose methotrexate and followed up in the Rheumatology Department, at Sohag University. Patients and Methods: A retrospective, record-based study. All cases with rheumatoid arthritis were treated with low-dose methotrexate for at least 3 months and were recorded in the files of the Rheumatology Department, Sohag University Hospitals, in the period from 1 Jan 2012 to 31 December 2021. The files of the selected cases were revised carefully regarding details of the demographic data, clinical history, comorbidities, and side effects and toxicities supposed to be due to methotrexate. Results: The study included the files of 1077 rheumatoid arthritis cases. 849 cases (78.8%) were chronic MTX users, and 228 cases (21.2%) were non-chronic MTX users, taken as the control group. The comparison between MTX users and non-users as regards the clinical data revealed that MTX users had less disease duration, more morning stiffness, and less hypertension. MTX use was significantly associated with a higher incidence of gastritis, blurred vision, anemia, pneumonitis, and hepatotoxicity. Conclusion: Although generally tolerable in low doses, MTX is sometimes associated with some toxicities including gastritis, blurred vision, anemia, pneumonitis, and hepatotoxicity.