Purpose <p>To evaluate perioperative and long-term outcomes of extended totally extraperitoneal repair (eTEP) repair for midline ventral hernias, comparing procedures performed with versus without posterior rectus sheath (PRS) closure.</p> Methods <p>A systematic review was performed according to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. After PROSPERO registration (CRD420251083420), a search was performed in MEDLINE, Embase, and Web of Science databases for studies published up to April 2025. Articles were excluded if patients underwent concomitant transversus abdominal muscle release.</p> Results <p>Five-hundred-fifty-five and 557 patients underwent eTEP without and with PRS closure, respectively. Patient and hernia characteristics were comparable between groups, with most defects appearing to fall within the W1-W2 range according to the European Hernia Society classification. The comparison between the non-closure and closure group showed statistically significant differences in the intraoperative peritoneal tears (2.2% versus 0.5% in the non-closure and closure group, respectively, <i>p</i> = 0.0189), impossibility to close the peritoneum (0.7% versus 0 in the non-closure and closure group, respectively, <i>p</i> = 0.0447), and conversion to open surgery (0.7% versus 0 in the non-closure and closure group, respectively, <i>p</i> = 0.0447). No differences in postoperative interparietal hernias occurred between the two groups.</p> Conclusion <p>Evidence comparing PRS non-closure and closure during eTEP repair remains limited and heterogeneous. Both approaches appear safe and effective, showing comparable intra- and postoperative outcomes; importantly, PRS closure is not associated with an increased risk of interparietal hernias. Current data do not justify a standardized recommendation, and the choice should be individualized based on defect characteristics and surgeon experience.</p>