Objective We investigated the effect of prognostic nutritional index on the prognosis of patients experiencing their first relapse of multiple myeloma.Methods A retrospective analysis was conducted on 101 patients experiencing their first relapse of multiple myeloma, who were treated at Suining Central Hospital from March 2016 to June 2023 The optimal cut-off value was determined using the receiver (ROC) curve based on the patients' work characteristics. Prognostic nutritional index was grouped with a cut-off value of 41.9 to analyze the differences between the two groups in terms of age, sex, serum calcium, hemoglobin, creatinine, lactate dehydrogenase, and ISS staging and to identify the prognostic factors influencing patients with multiple myeloma. Results Prognostic nutritional index was found to be an independent factor affecting overall survival. Univariate analysis revealed the factors affecting overall survival in multiple myeloma, including blood calcium, lactate dehydrogenase, extramedullary plasmacytoma, physical fitness status score, prognostic nutritional index at the time of the initial diagnosis, and prognostic nutritional index after two treatment courses following the first relapse （P＜0.005）. Multivariate analysis showed that prognostic nutritional index at the initial diagnosis (hazards ratio ［HR］=0.41, 95% confidence interval［CI］: 0.18-0.93) and prognostic nutritional index after two treatment courses following the first relapse (HR=0.33, 95% CI:0.14-0.78) were independent risk factors.Conclusion A low prognostic nutritional index indicates an unfavorable prognosis in patients with multiple myeloma during their first relapse