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Background: Methotrexate is an immunomodulatory therapy that may offer benefit to patients with hidradenitis suppurativa (HS). Despite its theoretical advantages, there is a paucity of available data regarding long-term methotrexate use in patients with HS. Objective: This study aimed to assess whether methotrexate treatment leads to improvement in HS disease severity. Methods: We conducted an institutional review board–approved, single-center, retrospective chart review of patients with HS who were treated with methotrexate between 2000 and 2018. Primary outcome measurements included the HS Physician's Global Assessment (HS PGA), Hurley staging, abscess count, fistula count, and inflammatory nodule count. Results: A total of 29 patients were identified; 14 were excluded for reasons including never starting methotrexate and missing follow-up data. For remaining patients (n = 15), the average cumulative dose of methotrexate was 520.1 mg (range, 30–1665 mg) and the average length of treatment was 11.7 months (range, 1–38 months). Patients taking methotrexate as a primary therapy had a higher cumulative dose and length of treatment (520.13 mg; 14.6 months) compared with those taking biologics concomitantly (468.44 mg; 9.1 months). Patients using methotrexate as primary therapy demonstrated nonsignificant reductions in HS PGA, inflammatory nodule count, and abscess count. Patients on concomitant biologic therapy failed to demonstrate any change in HS PGA, inflammatory nodule count, and abscess count. Limitations: Limitations of the study include its retrospective nature, small sample size, length of time on methotrexate between groups, and homogeneity of the patient population. Conclusion: Methotrexate may represent an effective treatment option in older patients with lower body mass indices but fails to offer benefit in patients taking concurrent biologic therapy.