Background Acute appendicitis is the commonest surgical emergency, but its diagnosis can be elusive with a negative appendicectomy rate of 20%. The aims of this study were to investigate the potential value of the markers of acute inflammation, serum amyloid A (SAA), and serum procalcitonin (ProCT), in the diagnosis of acute appendicitis in adults and to compare that with the commonly used serum C-reactive protein (CRP). Methods Adult patients presenting with acute right lower abdominal pain and a clinical suspicion of acute appendicitis were included. Blood samples were obtained within 6 hours of admission for rapid serum CRP assay and for end-of-recruitment batch analysis of SAA and serum ProCT concentrations. Results A total of 147 patients (81 males) with a mean (±SD) age of 36 (±17) years were recruited. Appendicitis was confirmed histologically in 61 of 72 patients (84.7%) who underwent appendicectomy. A post hoc analysis revealed a diagnostic sensitivity and specificity for SAA of 92% and 72%, ProCT of 85% and 74%, and CRP of 75% and 72%, respectively. The receiver operator characteristics for the area under the curves showed that SAA (P=0.011) and ProCT (P=0.037) significantly exceeded CRP in the prediction of acute appendicitis on admission. Conclusions The measurement of SAA and serum ProCT on admission in patients with clinically suspected acute appendicitis seems to outperform serum CRP in aiding that diagnosis.