Background <p>Radical prostatectomy (RP) is associated with moderate to severe postoperative dynamic pain. In this study, we aimed to evaluate the effect of erector spinae plane block (ESPB) on postoperative Quality of Recovery (QoR), opioid consumption and pain scores in patients who underwent open RP.</p> Methods <p>This prospective randomized controlled study included 52 patients who underwent open RP. Patients were randomized into Group E (<i>n</i> = 26) with ESPB and Group W (<i>n</i> = 26) with wound infiltration. Patient QoR was measured preoperatively and postoperatively using a 40-item QoR-40 questionnaire. Additionally, tramadol consumption, nausea and vomiting, visual analog scale (VAS), sedation, and hemodynamic parameters were evaluated.</p> Results <p>The preoperative and postoperative results of the global QoR-40 questionnaire were statistically similar between the groups (<i>p</i> = 0.407). Postoperative VAS_Rest and VAS_Movement were similar between the groups (<i>p</i> = 0.313 and <i>p</i> = 0.161, respectively). Tramadol consumption was lower in Group E at 2 and 24&#xa0;h (<i>p</i> = 0.035 and <i>p</i> = 0.017, respectively). Intraoperative remifentanil consumption was significantly lower in Group E (<i>p</i> = 0.005). Complications, such as intraoperative bradycardia, hypotension, and bradycardia-hypotension, were more common in Group E (<i>p</i> = 0.001). Postoperatively, complications such as sedation, nausea, and vomiting, and the need for antiemetics were similar between the groups.</p> Conclusion <p>ESPB did not improve the quality of postoperative recovery in patients who underwent RP. However, ESPB reduced opioid consumption while postoperative pain scores remained similar.</p> Trial Registration <p>ClinicalTrials.gov, NCT05853133, Date of registration: 02/05/2023.</p>