Background: Left ventricular reverse remodeling by cardiac resynchronization therapy (CRT) can significantly improve the prognosis for heart failure (HF) patients. The time course of CRT response remains poorly characterized. Method and Results: This retrospective study included 99 HF patients who received a CRT device at a single center from 2006 to 2017. CRT response was defined as ≥10% improvement in left ventricular ejection fraction on follow-up. They were divided into three groups: early responders (ERs): 49 patients with CRT response by the six-month follow-up; late responders (LRs): 17 patients with CRT response between six-month and three-years; and non-responders (NRs): 33 patients with no CRT response. The ERs and LRs had significantly lower rates of HF hospitalization and all-cause deaths than the NRs. Multivariate logistic regression analysis identified that narrower QRS duration before implantation (p = 0.046) and the presence of moderate to severe mitral regurgitation (MR) at the six-month follow-up (p = 0.035) as independent predictors of NRs. Conclusions: Regardless of the timing, HF patients who have CRT response have a better long-term prognosis than NRs. The Severity of MR can predict whether a patient with no response at the six-month follow-up will be NRs.