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Background Pancreas-specific lipase is reported to aid in diagnosing acute pancreatitis ( AP) in dogs but has not been rigorously evaluated clinically. Hypothesis/Objectives To describe variability of disease in dogs with suspected clinical AP, and to evaluate accuracy of 2 pancreatic-specific lipase immunoassays, Spec cPL (SPEC) and SNAP cPL (SNAP), in diagnosing clinical AP. We hypothesized that SPEC and SNAP provide better diagnostic accuracy than serum amylase or total lipase. Animals A total of 84 dogs; 27 without AP and 57 with clinical signs associated with AP. Methods Multicenter study. Dogs were prospectively enrolled based upon initial history and physical examination, then retrospectively classified into groups according to the likelihood of having clinical AP by a consensus of experts blinded to SPEC and SNAP results. Bayesian latent class analyses were used to estimate the diagnostic accuracy of SPEC and SNAP. Results The estimates for test sensitivities and specificities, respectively, ranged between 91.5-94.1% and 71.1-77.5% for SNAP, 86.5-93.6% and 66.3-77.0% for SPEC (cutoff value of 200 μg/L), 71.7-77.8% and 80.5-88.0% for SPEC (cutoff value of 400 μg/L), and were 52.4-56.0% and 76.7-80.6% for amylase, and 43.4-53.6% and 89.3-92.5% for lipase. Conclusions and Clinical Importance SNAP and SPEC have higher sensitivity for diagnosing clinical AP than does measurement of serum amylase or lipase activity. A positive SPEC or SNAP has a good positive predictive value ( PPV) in populations likely to have AP and a good negative predictive value ( NPV) when there is low prevalence of disease. [ABSTRACT FROM AUTHOR]