OBJECTIVES: The aim of this study was to evaluate the effect of continuous statin treatment on new-onset heart failure (HF) in patients with breast cancer receiving anthracycline-based chemotherapy. BACKGROUND: In vitro and animal model experimental studies have reported that statins prevent doxorubicin-induced cardiotoxicity. METHODS: A total of 628 women with newly diagnosed breast cancer (mean age 51.5 ± 10.8 years) treated with anthracycline were retrospectively identified and studied. The primary outcome (incident HF hospitalization) was compared in propensity-matched patients receiving uninterrupted statin therapy through the follow-up period of 2.55 ± 1.68 years and their counterparts not receiving continuous statin therapy. RESULTS: After propensity matching (2:1), the 67 patients (10.7%) receiving uninterrupted statin therapy were combined with 134 controls. New-onset HF was observed in 67 of the 201 matched patients. Multivariate-matched Cox regression analysis showed a significantly lower hazard ratio [HR] of 0.3 (95% confidence interval [CI]: 0.1 to 0.9; p = 0.03) for patients taking uninterrupted statin therapy. Cardiotoxicity risk factors at the time of cancer diagnosis (HR: 5.0; 95% CI: 2.2 to 11.1; p < 0.001), baseline ejection fraction <55% (HR: 2.7; 95% CI: 1.2 to 6.3; p = 0.02), and trastuzumab use (HR: 3.0; 95% CI: 1.3 to 7.2; p = 0.01) were predictors of incident HF. CONCLUSIONS: In this analysis of female patients with breast cancer treated with anthracycline chemotherapy, statin use was associated with a lower risk for incident HF. This finding is consistent with prior animal studies and warrants further investigation through prospective randomized clinical trials.