BACKGROUND: The factors affecting the quality of histopathologic specimens obtained via small intestinal endoscopic biopsy (SIEB) remain unclear. HYPOTHESIS/OBJECTIVES: To identify factors related to the quality of histopathologic specimens obtained via SIEB. ANIMALS: Histopathologic duodenal and ileal specimens were obtained from 116 dogs and 38 cats that underwent SIEB for diagnostic purposes. METHODS: This retrospective study analyzed 3354 individual histopathologic specimens scored using the grading system of histopathologic adequacy (GSHA). A lower GSHA score indicates lower quality specimens. Univariate and multivariate ordinal logistic models were used to assess the relationship between the GSHA score of the specimens and various explanatory factors, including fixation method, biopsy forceps size, biopsy site, and histopathologic diagnosis. The generalized estimating equation method was used to account for the clustering of specimens among animals. RESULTS: Multivariate models using the specimens showed that filter paper fixation of endoscopic samples resulted in a higher GSHA score than floating fixation in both dogs (ordinal odds ratio [OR]: 0.19
95% confidence interval [CI]: 0.15-0.25) and cats (ordinal OR: 0.19
95% CI: 0.13-0.29). In dogs, the scores were lower for duodenal specimens than for ileal specimens and for specimens obtained using smaller forceps. In cats, the scores were lower for ileal specimens than for duodenal specimens and for older animals. CONCLUSION AND CLINICAL IMPORTANCE: The quality of histopathologic specimens obtained via SIEB is influenced by the fixation method. Additionally, other factors differ between dogs and cats. These results contribute to improved SIEB practices in veterinary medicine.