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Acute appendicitis continues to constitute a diagnostic and therapeutic challenge. The aim of this study was to synthesize evidence from randomized controlled trials (RCTs) comparing nonoperative versus surgical management of uncomplicated acute appendicitis in adult patients.A systematic literature search of the PubMed, Cochrane, and Scopus databases was performed with respect to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement (end-of-search date: January 29, 2017). Data on the study design, interventions, participants, and outcomes were extracted by two independent reviewers. The random-effects model (DerSimonian-Laird) was used to calculate pooled effect estimates when substantial heterogeneity was encountered; otherwise, the fixed-effects (Mantel-Haenszel) model was implemented. Quality assessment of included RCTs was performed using the modified Jadad scale.Five RCTs were included in this review. Overall, 1,430 adult patients with uncomplicated acute appendicitis underwent either nonoperative (n = 727) or operative management (n = 703). Treatment efficacy at 1-year follow-up was significantly lower (63.8%) for antibiotics compared with the surgery group (93%) (risk ratio [RR], 0.68; 95% confidence interval [CI], 0.60–0.77; p < 0.001). Overall complications were significantly higher in the surgery group (166/703 [23.6%]) compared with the antibiotics group (56/727 [7.7%]) (RR, 0.32; 95% CI, 0.24–0.43; p < 0.001). No difference was found between the two treatment modalities in terms of perforated appendicitis rates (RR, 0.52; 95% CI, 0.14–1.92), length of hospital stay (weighted mean difference [WMD], 0.20; 95% CI, −0.16 to 0.56), duration of pain (WMD, 0.22; 95% CI, −5.30 to −5.73), and sick leave (WMD, −2; 95% CI, −5.2 to 1.1).Conservative management of uncomplicated appendicitis in adults warrants further study. Addressing patients’ expectations via a shared decision-making process is a crucial step in optimizing nonoperative outcomes.Systematic review, level II.