Context and objective: To evaluate if YKL-40 can provide prognostic information in patients with ischemic heart failure (HF) and identify patients who may benefit from statin therapy. Materials and Methods: The association between serum YKL-40 and predefined outcome was evaluated in 1344 HF patients assigned to rosuvastatin or placebo. Results: YKL-40 was not associated with outcome in adjusted analysis. In YKL-40 tertile 1, an effect on the primary outcome (HR 0.50, p = 0.006) and CV death (HR 0.54 p = 0.040) was seen by rosuvastatin in adjusted analysis. Conclusions: A beneficial modification of outcome was observed with statin therapy in patients with low YKL-40 levels.