Background <p>Postoperative ileus remains one of the most frequent barriers to timely recovery after colorectal resection, even in the modern era of minimally invasive surgery and enhanced recovery after surgery. Although alvimopan is designed to counteract opioid-mediated gastrointestinal dysmotility, its incremental benefit in contemporary minimally invasive colorectal surgery remains unclear. Existing studies have reported inconsistent effects on ileus prevention, length of stay, and hospitalization. Therefore, we performed a systematic review and meta-analysis of comparative studies evaluating perioperative alvimopan versus no alvimopan after elective colorectal resection in minimally invasive and enhanced recovery settings.</p> Methods <p>This systematic review and meta-analysis was conducted in accordance with the PRISMA 2020 and MOOSE recommendations and was registered in PROSPERO [CRD420261354171]. PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library were searched from inception to the final search date. Eighty-eight records were identified, 66 were screened after duplicate removal, nine full texts were assessed, and five comparative studies were included in the analysis. The primary outcome was the incidence of postoperative ileus. The secondary outcomes were length of hospital stay and readmission rate. Random-effects meta-analyses were performed.</p> Results <p>Five retrospective comparative studies comprising 1,379 patients were included, of whom 698 received alvimopan, and 681 did not. Alvimopan was associated with a borderline reduction in postoperative ileus compared with no alvimopan (23/672 [3.4%] vs. 46/617 [7.5%]; RR 0.43, 95% CI 0.18–0.99), although this finding was not robust in leave-one-out sensitivity analysis after removal of the most influential study. Length of hospital stay numerically favored alvimopan but was not statistically significant in the primary pooled analysis (MD -0.63 days, 95% CI -1.27 to 0.02), and readmission was also not significantly different between groups (21/698 [3.0%] vs. 23/681 [3.4%]; RR 0.89, 95% CI 0.48–1.64). The GRADE certainty of evidence was very low across all outcomes.</p> Conclusions <p>In minimally invasive colorectal surgery performed within enhanced recovery pathways, alvimopan may reduce postoperative ileus, but this signal was borderline, sensitivity-dependent, and supported only by very low-certainty retrospective evidence. Current evidence does not support a consistent benefit for length of stay or readmission. Alvimopan should therefore be interpreted as a possible selective adjunct for ileus prevention rather than a routine recovery-enhancing strategy.</p> Trial registration <p>PROSPERO registration number [CRD420261354171].</p>