BackgroundThis study aimed to analyze the systemic-immune inflammation index (SII)’s diagnostic performance in diagnosing acute appendicitis (AA) and discriminating between complicated acute appendicitis (CAA) and non-complicated acute appendicitis (NCAA).MethodsThis review was registered in PROSPERO (CRD42024587430). We included prospective or retrospective original clinical studies evaluating the diagnostic performance of SII in AA. A search was conducted in PubMed, Web of Science, Scopus, and OVID. Search terms and keywords were: (appendicitis OR appendectomy) AND (systemic-immune inflammation index OR SII). Two independent reviewers selected the articles and extracted relevant data. Methodological quality was assessed using the QUADAS2 index. A synthesis of the results, standardization of the metrics, four random-effect meta-analyses, and two Diagnostic Test Accuracy (DTA) meta-analyses were performed.ResultsThirteen studies with data from 9083 participants, including 5255 patients with a confirmed diagnosis of AA and 3828 controls (CG), were included in this review. The random-effect meta-analysis of SII (AA vs. CG) included ten articles (3733 AA and 3510 controls) and resulted in a significant mean difference [95% CI] of 1072.46 [750.55,1394.37] (p<0.001). The random-effect meta-analysis of SII (CAA vs. NCAA) included nine articles (1116 CAA and 2984 NCAA) and resulted in a significant mean difference [95% CI] of 1294.2 [731.54,1856.86] (p<0.001). Subgroup meta-analysis for studies conducted in pediatric-only populations maintained statistical significance. The DTA meta-analysis (AA vs. CG) yielded a pooled sensitivity and specificity [95% CI] of 81.8 [75.2,86.9] % and 79.9 [68.2,88.1] %. The DTA meta-analysis (NCAA vs. CAA) resulted in a pooled sensitivity and specificity [95% CI] of 72.5 [49.6,87.6] % and 82.5 [65.1,92.2] %.ConclusionsSII emerges as a robust tool for diagnosing AA and differentiating between NCAA and CAA. The retrospective nature of most of the included studies and their limited geographical distribution warrant further prospective multicenter studies to validate these findings.FundingNoneRegistrationPROSPERO (CRD42024587430).