Background Multiple myeloma (MM) is a malignant clonal disease originating from plasma cells. Patients with MM are prone to infections due to factors such as impaired immune function, bone marrow suppression, and anticancer therapy. A systematic review and meta-analysis of risk factors for infections in patients with MM provides evidence-based guidance for clinical risk assessment and intervention. Methods Search databases such as PubMed, Web of Science, Embase, Cochrane Library, from the establishment of the database to July 20, 2025, to include observational studies evaluating risk factors for infection in patients with MM. Use the NOS tool for literature quality assessment and perform meta-analysis using Stata 15.0 to combine odds ratios (OR) and 95% confidence intervals (CI). Results This study included 15 articles (1 case-control study and 14 cohort studies), involving 4,717 participants. The results of this meta-analysis suggest that age 65 OR = 1.72, 95% CI (1.18, 2.48), male OR = 1.70, 95% CI (1.11, 2.62), smoking OR = 2.97, 95% CI (1.94, 4.57), International Staging System III OR = 2.22, 95% CI (1.81, 2.73), diabetes OR = 2.67, 95% CI (1.74, 4.09), immunomodulatory drugs OR = 3.40, 95% CI (2.29, 5.07), hemoglobin 10 g/dLOR = 2.28, 95% CI (1.65, 3.16), creatinine ≥ 2 mg/dLOR = 2.80, 95% CI (2.07, 3.79) was significantly associated with infection in patients with multiple myeloma. Conclusion This systematic review and meta-analysis indicate that age 65 years, male gender, smoking, ISS stage III, diabetes, use of immunosuppressive agents, hemoglobin 10 g/dL, and creatinine ≥2 mg/dL are all significant risk factors for infection in MM patients. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420251065706
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