Blood concentration of galectin-3 (Gal-3) - a biomarker of fibrosis useful in diagnostics and prognostication in heart failure (HF) - is known to be elevated in patients with renal impairment, a condition which often accompanies cardiac insufficiency. To investigate the effect of moderately reduced renal function (estimated glomerular filtration rate (eGFR) 30-60 mL/min/1.73 m2) on the diagnostic and prognostic utility of circulating Gal-3 in patients with HF with preserved ejection fraction (HFpEF). Clinical, biochemical and echocardiographic variables were collected at baseline in 154 patients with HFpEF: 101 with normal and 53 with moderately reduced renal function, who were followed up for 48 (24-60) months for HF hospitalization and cardiovascular (CV) death (composite endpoint). Patients with moderately impaired renal function were characterized by higher age, Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score, Gal-3, B-type natriuretic peptide (BNP) and New York Heart Association (NYHA) class, lower hemoglobin, and more advanced left ventricular diastolic dysfunction. Older age, female sex and deeper impairment of renal performance were determinants of higher Gal-3 blood concentrations. Lower exercise capacity (lower peak VO2) was associated with higher Gal-3 level and more pronounced renal impairment. Multivariable regression analysis demonstrated the significance of renal dysfunction as a determinant of lower exercise capacity and revealed a significant interaction between Gal-3 and eGFR with respect to peak VO2. The addition of Gal-3 to the prognostic models based on clinical data improved their predictive power for the study endpoint. The Kaplan-Meier analysis revealed that the presence of moderately reduced renal function with eGFR 30-60 mL/min/1.73 m2 did not enhance the increased risk of adverse outcome associated with Gal-3 above the median. In patients with HFpEF, the coexistence of moderate renal dysfunction does not deteriorate the prognostic usefulness of circulating Gal-3. However, renal impairment modifies the association between Gal-3 and exercise capacity, which supports the need to adjust for kidney function when interpreting the contribution of Gal-3 to exercise intolerance in this population.