ABSTRACT: OBJECTIVES:Small intestinal bacterial overgrowth (SIBO) is often present in patients with chronic pancreatitis (CP) with persistent steatorrhea, despite pancreatic enzyme replacement therapy. Overall prevalence of SIBO, diagnosed by glucose breath test (GBT), varies between 0% and 40% but 0%-21% in those without upper gastrointestinal (GI) surgery. We investigated the prevalence and nonsurgical independent predictors of SIBO in CP without upper GI surgery. METHODS:Two hundred seventy-three patients ?18 years old had a presumptive diagnosis of CP and a GBT between 1989 and 2017. We defined CP by Mayo score (0-16) ?4 and a positive GBT for SIBO by Rome consensus criteria and retrospectively collected data for 5 a priori variables (age, opiates, alcohol use, diabetes mellitus (DM), gastroparesis) and 41 investigational variables (demographics, GI symptoms, comorbidities, CP etiologies and cofactors, CP symptom duration, Mayo score and nondiabetes components, and biochemical variables). RESULTS:Ninety-eight of 273 patients had definite CP and 40.8% had SIBO. Five of 46 variables predicted SIBO: opiates, P = 0.005; DM, P = 0.04; total Mayo score, P < 0.05; zinc, P = 0.005; and albumin, P < 0.05). Multivariable analysis of 3 noncorrelated variables identified zinc level (odds ratio = 0.0001; P = 0.03) as the sole independent predictor of SIBO (model C-statistic = 0.89; P < 0.001). DISCUSSION:SIBO, diagnosed by GBT, occurs in 40.8% of patients with CP without upper GI surgery. In patients with CP, markers of more severe CP (low zinc level, DM and increased Mayo score) and opiate use should raise clinical suspicion for SIBO, particularly in patients with persistent steatorrhea or weight loss despite pancreatic enzyme replacement therapy.