Background The data on the prognostic values of high sensitivity C-reactive protein (hsCRP) levels in patients with advanced symp-tomatic heart failure (HF) receiving cardiac resynchronization therapy (CRT) are scarce. The aim of present study was to investigate the association of serum hsCRP levels with left ventricle reverse remodeling after six months of CRT as well as long-term outcome. Methods A total of 232 CRT patients were included. The assessment of hsCRP values, clinical status and echocardiographic data were performed at baseline and after six months of CRT. Long-term follow-up included all-cause mortality and hospitalizations for HF. Results During the mean follow-up periods of 31.3 ± 31.5 months, elevated hsCRP (>3 mg/L) prior to CRT was associated with a significant 2.39-fold increase (P=0.006) in the risk of death or HF hospitalizations. At 6-month follow-up, patients who responded to CRT showed significant reductions or maintained low in hsCRP levels (–0.5 ± 4.1 mg/L reduction) compared with non-responders (1.7 ± 6.1 mg/L increase, P=0.018). Com-pared with patients in whom 6-month hsCRP levels were reduced or remained low, patients in whom 6-month hsCRP levels were increased or maintained high experienced a significantly higher risk of subsequent death or HF hospitalizations (Log-rank P<0.001). The echocardio-graphic improvement was also better among patients in whom 6-month hsCRP levels were reduced or remained low compared to those in whom 6-month hsCRP levels were raised or maintained high. Conclusions Our findings demonstrated that measurement of baseline and follow-up hsCRP levels may be useful as prognostic markers for timely potential risk stratification and subsequent appropriate treatment strategies in patients with advanced HF undergoing CRT.