Objectives: Genetically targeted treatment for heart failure is a one of promising treatment strategies. This study is to analyse the association between genetic variations in the beta-1 or beta-2 adrenergic receptor (AR) genes and G protein-coupled receptor kinases (GRK) gene and the effects of bisoprolol as beta-blockade in Korean patients with stable CHF. Methods: We enrolled 100 patients in chronic HF and left ventricular systolic dysfunction who were treated with ACEI or ARB, and/or diuretic medications. This was a prospective, multicenter, single arm clinical trial, and the titration of the dose of bisiprolol was according to CIBIS-II clinical trial fashion. And we genotyped 4 polymorphisms in 3 genes: ADRB1 (Arg389Gly), ADRB2 (Gly16Arg, Gln27Glu), and GRK5 and performed a multivariable clinical-genetic analysis. Echocardiography, 6 minutes walking test (MWT), Pro-NT BNP was determined before and after 6 months of bisoprolol therapy. Results: The interim analysis of the study (n=72) showed that the most common frequency of genetic variations were Arg389Arg in ADRB1, Arg16Gly and Gln27Glu in ADRB2, GRK5-Arg304 in GRK5. Bisoprolol resulted in a significant decrease in heart rate and increase in LVEF and 6MWT in ADRB1 (Arg389Arg), ADRB2 (Arg16Arg) and GRK5 (Arg304) group. No responder group of beta-blocker were ADRB1 (Gly389Gly) and GRK5 (His304). Conclusions: Bisoprolol were more effective in ADRB1 (Arg389Arg) or ADRB2 (Arg16Arg) adrenergic receptor phenotype or GRK5 (Arg304) phenotype in Korean HF patients. (clinicaltrials.gov NCT01104558).