Purpose Despite improvements of strategy in radical retropubic prostatectomy, blood loss is still a major concern. The lymphocyte/monocyte (LM) ratio is a prognostic indicator for various diseases. We identified the risk factors, including the LM ratio, for red blood cell (RBC) transfusion during radical retropubic prostatectomy. Methods This retrospective study assessed patients who underwent radical retropubic prostatectomy between March 2009 and December 2020. To determine the risk factors for RBC transfusion, a multivariate logistic regression analysis was conducted. A receiver operating characteristic (ROC) curve analysis was also performed. Postoperative outcomes, including acute kidney injury (AKI), hospitalization duration, and intensive care unit (ICU) admission, were also evaluated. Results Among 1302 patients, 158 patients (12.1%) received an intraoperative RBC transfusion. Multivariate logistic regression analysis demonstrated that the risk factors for RBC transfusion were the LM ratio, hemoglobin, 6% hydroxyethyl starch amount, and positive surgical margin. The area under the ROC curve of LM ratio was 0.706 (cut-off = 4.3). The LM ratio at ≤ 4.3 was significantly related to transfusion in multivariate-adjusted analysis (odds ratio = 4.598, P < 0.001). AKI and ICU admission were significantly higher, and the hospitalization duration was significantly longer in patients with RBC transfusion. Conclusions The LM ratio was a risk factor for RBC transfusion in radical retropubic prostatectomy. The optimal cut-off value of the LM ratio to predict transfusion was 4.3. RBC transfusion was associated with poor postoperative outcomes. Therefore, our results suggest that the LM ratio provide useful information on RBC transfusion in radical retropubic prostatectomy.