BACKGROUND Recent evidence endorses gut microbiota dysregulation in the pathophysiology of heart failure (HF). Small intestinal bacterial overgrowth (SIBO) might be present in HF and associated with poor clinical outcomes. Lactulose breath testing is a simple noninvasive test that has been advocated as a reliable indicator of SIBO. In patients with HF, we aimed to evaluate the association with clinical outcomes of the exhaled hydrogen (H2) and methane (CH4) concentrations through the lactulose breath test. RESULTS We included 102 patients with HF in which lactulose SIBO breath tests were assessed. Cumulative gas was quantified by the area under the receiver operating characteristic curve of CH4 (AUC-CH4) and H2 (AUC-H2). Clinical end points included the composite of all-cause death with either all-cause or HF hospitalizations, recurrent all-cause hospitalizations, and recurrent HF hospitalizations. Medians (interquartile ranges) of AUC-H2 and AUC-CH4 were 1290 U (520-2430) and 985 U (450-2120), respectively. In multivariable analysis, AUC-H2 (per 1000 U) was associated with all-cause death/all-cause hospitalization (hazard ratio [HR] 1.21, 95% CI 1.04-1.40; P = .012), all-cause death/HF hospitalization (HR 1.20, 95% CI 1.03-1.40; P = .021), and an increase in the rate of recurrent all-cause (incidence rate ratio [IRR] 1.31, 95% CI 1.14-1.51; P < .001) and HF (IRR 1.41, 95% CI 1.15-1.72; P = .001) hospitalizations. AUC-CH4 was not associated with any of these end points. CONCLUSIONS AUC-H2, a safe and noninvasive method for SIBO estimation, is associated with higher risk of long-term adverse clinical events in patients with HF. In contrast, AUC-CH4 did not show any prognostic value.