OBJECTIVE : To investigate the diagnostic potential of the concentrations of acute-phase proteins serum amyloid A (SAA), haptoglobin (Hp), and fibrinogen in blood and peritoneal fluid (PF) for differentiating horses with inflammatory colic (entero-colitis and peritonitis) from those with surgical colic. DESIGN : Prospective observational multicenter study. SETTING : Two university referral hospitals. ANIMALS : Horses referred for severe acute abdominal pain to Hospital 1 (n = 148) or Hospital 2 (n = 78). INTERVENTION : Blood and PF samples collected at admission were used for acute-phase protein concentration measurement. MEASUREMENTS AND MAIN RESULTS : Blood and PF samples collected at admission were used for acute-phase protein concentration measurement. CONCLUSIONS : Evaluation of SAA in serum improved the ability to differentiate horses with acute inflammatory colic requiring medical treatment from horses with colic requiring surgery, as it allowed an additional 4% of horses to be correctly classified into medical and surgical cases. Improved differentiation of these 2 groups of horses with colic may minimize the risk of unnecessary or delayed surgery.