Background Predicting non‐survival in horses with acute colitis improves early decision making. Therefore, this study aimed to determine the prognostic value of serum amyloid A (SAA) and other clinicopathological and clinical variables in adult horses with acute colitis. Methods Clinical variables, SAA and other blood biomarkers, including plasma L‐lactate (lactate), were assessed in 176 horses with acute colitis. A multivariate model for the prediction of non‐survival was constructed. Icelandic horses were analysed separately. Results Admission SAA was similar in survivors (median 548 mg/L; range 0–5453 mg/L) and non‐survivors (396 mg/L; 0–5294) (p = 0.43). A model for non‐survival included year of admission, lactate, heart rate, age and colic duration of more than 24 hours. Icelandic horses had a relative risk of 2.9 (95% confidence interval = 2.2–3.8) for acute colitis compared to other breeds. Lactate in Icelandic horses was higher than that in other breeds in both survivors (4.0 mmol/L, range 1.0–12.7 vs. 2.0, 0.7–12.5) and non‐survivors (10.0, 1.5–26 vs. 5.4, 0.8–22) (p < 0.001). Limitations The prognostic value of repeated measurements of SAA could not be assessed in this study, as 71% of the non‐surviving horses died within a day of admission. Conclusion Admission SAA did not predict non‐survival. Breed needs consideration when lactate is evaluated as a predictor for non‐survival in horses with colitis.