<![CDATA[Introduction: Surgical site infection (SSI) is the leading preventable complication after appendectomy for complicated (gangrenous, perforated, or abscess-forming) appendicitis. Perioperative antibiotic prophylaxis is established; however, whether prolonging postoperative antibiotics adds benefit and which patient- and operation-related factors drive SSI remain contested. We synthesized the efficacy of prolonged versus short-course prophylaxis and the factors associated with SSI. Methods: Following PRISMA 2020, we searched MEDLINE, Embase, and CENTRAL to July 2026 for studies of patients undergoing appendectomy for complicated appendicitis that reported SSI. Randomized and cohort studies comparing short versus extended postoperative antibiotics were pooled as risk ratios (RR); adjusted odds ratios (OR) for factors associated with SSI were pooled by inverse-variance random-effects (DerSimonian–Laird) models. Heterogeneity (I²), prediction intervals, leave-one-out analyses, and Egger's test were assessed. Results: Eleven studies (4,135 patients) were included in the analysis. Prolonging antibiotics beyond a short course did not reduce incisional SSI (randomized trials: RR 1.91, 95% CI 0.90–4.03; all studies: RR 1.12, 95% CI 0.54–2.36, I²=34%) or intra-abdominal abscesses (RR 1.00, 95% CI 0.71–1.42, I²=0%). Three factors were independently associated with SSI: complicated/perforated pathology (OR 4.75, 95% CI 2.81–8.04), open versus laparoscopic approach (OR 2.41, 95% CI 1.22–4.77), and prolonged operative duration (OR 2.68, 95% CI 1.75–4.11). Conclusion: Prophylaxis is essential in complicated appendicitis, but it need not be prolonged; extending beyond a course does not reduce SSI or intra-abdominal abscesses, supporting stewardship. The SSI burden reflects disease severity, open approach, and prolonged operations, guiding risk-adapted prevention over longer courses.]]>
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