This study characterized CXC chemokine receptor 4 (CXCR4) expression in patients with mitral valve disease and chronic atrial fibrillation (AF). Forty-eight patients with chronic AF formed two groups based on whether they were treated with or without renin-angiotensin system (RAS) blockers (AF + RAS group; n = 25, or AF -RAS group; n = 23). The controls comprised 17 mitral valve disease patients with sinus rhythm (SR group). CXCR4 mRNA and protein levels in the left atria were significantly higher in the AF -RAS and AF + RAS groups than in the SR group. CXCR4 expression was significantly lower in the AF + RAS group than the AF -RAS group. More CD34 + cells expressed CXCR4 in the AF -RAS and AF + RAS groups than in the SR group. Angiotensin II, collagen I and left atrial diameter significantly positively correlated with CXCR4 expression in the AF -RAS group. These results suggest that CXCR4 expression is up-regulated in chronic AF patients with mitral valve disease, is associated with atrial remodelling, and that these effects are attenuated by RAS blockers.