Aims: To investigate whether plasma galectin-3, a mediator of fibrogenesis, can identify patients with chronic heart failure (HF) for whom statins are effective. Methods and results: Patients with ischaemic systolic HF enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) were randomly assigned to 10 mg/day of rosuvastatin or placebo. Galectin-3 was measured in plasma. The primary outcome was cardiovascular death, myocardial infarction, or stroke. Of 1492 patients, 411 had a primary event during a median follow-up of 32.8 months. There was an interaction between baseline galectin-3 and rosuvastatin on the primary endpoint (P-value for interaction = 0.036). Among patients with below the median plasma concentrations of galectin-3 (≤19.0 ng/mL), those assigned to rosuvastatin had a lower primary event rate [hazard ratio (HR) 0.65; 95% confidence interval (CI), 0.46–0.92; P= 0.014], lower total mortality (HR 0.70; 95% CI, 0.50–0.98; P= 0.038), and lower event rate of all-cause mortality and HF hospitalizations (HR 0.72; 95% CI, 0.54–0.98; P= 0.017) compared with placebo, but no benefit was observed in patients with higher levels of galectin-3. The combination of concurrently low concentrations of galectin-3 and N-terminal pro-B-type natriuretic peptide (<102.7 pmol/L) identified patients with a large benefit with rosuvastatin (HR 0.33; 95% CI, 0.16–0.67; P= 0.002). Conclusion: Patients with systolic HF of ischaemic aetiology who have galectin-3 values <19.0 ng/mL may benefit from rosuvastatin treatment. However, the data from this post hoc analysis should be interpreted with caution since the overall results of the CORONA study did not show a significant effect on the primary endpoint.