Background: Serum amyloid A has been widely reported as a useful biochemical marker in the diagnoses of acute appendicitis. The aim of this study was to appraise the diagnostic accuracy of serum amyloid A in the diagnosis of acute appendicitis. Methods: A systematic search of several databases was conducted. The search time was from the beginning of the databases creation to March 1, 2021, and the languages were restricted to English and Chinese. Clinical studies using serum amyloid A for the diagnosis of acute appendicitis were included. The overall sensitivity and specificity were calculated by using a bivariable mixed effects model. Heterogeneity was tested using I2 statistics. This study has been registered on the International Prospective Register of Systematic Reviews (PROSPERO; no. CRD42021241343). Results: Five studies comprising 668 participants were eligible for inclusion. The overall sensitivity and specificity of serum amyloid A in diagnosing acute appendicitis were 0.87 (95% confidence interval [CI], 0.79-0.92) and 0.74 (95% CI, 0.59-0.85), respectively. The positive and negative likelihood were 3.3 (95% CI, 2.1-5.4) and 0.18 (95% CI, 0.11-0.28), respectively. The area under the summary receiver operating characteristic curves was 0.89 (95% CI, 0.86-0.91). The heterogeneity was significant (I2 = 82%; 95% CI [63%-100%]). Conclusions: Serum amyloid A has good diagnostic accuracy for acute appendicitis. It is expected that serum amyloid A could be helpful in the early clinical diagnosis of acute appendicitis.