Cardiac fibrosis is associated with heart failure and poor prognosis. Fibrosis biomarkers have been poorly evaluated as a tool to predict cardiac resynchronization therapy (CRT) response generating conflicting results. The present study assessed the predictive value of cardiac fibrosis biomarkers on CRT response. Patients underwent clinical examination, echocardiography and blood fibrosis biomarker evaluation prior to CRT implantation. At six months, a positive response to CRT was defined by a composite endpoint of no death or hospitalization for heart failure, and presence of left ventricular (LV) reverse remodeling (decrease in LV end-systolic volume ≥15%). Sixty patients were included in a multicenter study. At 6 months, 38 were positive responders to CRT and reached the response criteria (63%). Compared to non-responders, CRT responders displayed lower concentration levels of the fibrosis biomarkers procollagen type I C-terminal propeptide [PICP 135[99-166] ng/ml vs. 179[142-226]ng/ml, p = 0.001)] and procollagen type III N-terminal propeptide [PIIINP 5.50[3.66-8.96] ng/ml vs. 8.01[5.01-11.86]ng/ml, p = 0.014)] at baseline. In multivariate analysis, a PICP ≤ 163 ng/ml was associated with a positive CRT response [OR = 7.8(1.3-46.7), p = 0.023] independently of the presence of LBBB, QRS duration, LV lead position or non-ischemic cardiomyopathy. Altogether, the present findings show that a lower degree of cardiac fibrosis is associated with a positive response after CRT implantation. PICP evaluation before CRT implantation could help improve patient selection.