Purpose In previous studies in different clinical scenarios, probiotics can help to modulate inflammatory cytokines and impact in clinical outcomes. Heart failure presents an intense inflammatory profile that is related to worse outcomes. We have scarce information about the impact of probiotic supplementation in heart failure. Methods In this randomized, double-blind, placebo-controlled clinical trial, we randomly assigned 57 outpatients with functional class III or IV, or that were included in heart transplant waiting list, to receive probiotic Lactobacillus acidophilus LA14 (at a dose of 1x109 CFU once a day) or placebo. The primary outcome was the impact in plasmatic levels of TNF-α. Secondary outcomes included the influence of probiotic in other inflammatory cytokines (interleukins (IL) 1,6), lipopolysaccharide (LPS) and clinical outcomes as hospitalizations, transplantation and death. Results After six months follow-up, there were no evidence of effect of probiotic in plasmatic levels of TNF- α (4,55 x 5,18pg/mL, p=0,294) and other cytokines (IL1 3,9 x 3,12 pg/mL, p=0,688; IL6 1,21 x 1,19 pg/mL, p= 0,915) and LPS (1,39 x 1,81 pg/mL, p=0,708). Probiotic also did not exert impact on hospitalization (relative risk, 1,1; 95% CI, 0,28 to 2,7, p=0,81), transplantation (relative risk, 1,1; 95% CI; 0,13 to 6,55, p= 0,94) and mortality (relative risk, 1,1; 95% CI, 0,18 to 4,51, p= 0,91). Conclusion Probiotic supplementation in outpatients with advanced heart failure did not impact in plasmatic levels of inflammatory cytokines, LPS and clinical outcomes. In previous studies in different clinical scenarios, probiotics can help to modulate inflammatory cytokines and impact in clinical outcomes. Heart failure presents an intense inflammatory profile that is related to worse outcomes. We have scarce information about the impact of probiotic supplementation in heart failure. In this randomized, double-blind, placebo-controlled clinical trial, we randomly assigned 57 outpatients with functional class III or IV, or that were included in heart transplant waiting list, to receive probiotic Lactobacillus acidophilus LA14 (at a dose of 1x109 CFU once a day) or placebo. The primary outcome was the impact in plasmatic levels of TNF-α. Secondary outcomes included the influence of probiotic in other inflammatory cytokines (interleukins (IL) 1,6), lipopolysaccharide (LPS) and clinical outcomes as hospitalizations, transplantation and death. After six months follow-up, there were no evidence of effect of probiotic in plasmatic levels of TNF- α (4,55 x 5,18pg/mL, p=0,294) and other cytokines (IL1 3,9 x 3,12 pg/mL, p=0,688; IL6 1,21 x 1,19 pg/mL, p= 0,915) and LPS (1,39 x 1,81 pg/mL, p=0,708). Probiotic also did not exert impact on hospitalization (relative risk, 1,1; 95% CI, 0,28 to 2,7, p=0,81), transplantation (relative risk, 1,1; 95% CI; 0,13 to 6,55, p= 0,94) and mortality (relative risk, 1,1; 95% CI, 0,18 to 4,51, p= 0,91). Probiotic supplementation in outpatients with advanced heart failure did not impact in plasmatic levels of inflammatory cytokines, LPS and clinical outcomes.