Background: Safe and effective therapeutic management of refractory coronary artery disease (CAD) in heart patients is critical to enhance cardiovascular function and improve quality of life. Current therapies for refractory CAD are inadequate in ameliorating angina and promoting revascularization of ischemic myocardium. Hypothesis: Cardiac shock wave therapy (CSWT) is a safe and effective noninvasive intervention in the management of patients with refractory CAD. Methods: The study enrolled 9 male patients age 50 to 70 years (5.11 +/- 5.46 years) with a diagnosis of CAD and stent implantation (3.00 +/- 2.24 stents). CSWT was carried out for 3 months at 3 intervals during the first week of each month (first, third, and fifth day), for a total of 9 therapies per patient. Dobutamine stress echocardiography and radionuclide angiography identified the myocardial ischemic segments. The effects of CSWT on myocardial perfusion and systolic function were examined. Other outcome measures included myocardial injury enzyme markers, angina scale, nitroglycerin dosage, and cardiopulmonary fitness assessments. Results: Improved myocardial blood flow and regional systolic function (stress peak systolic strain rate -1.10 to -1.60 s(-1), P = 0.002) were detected in patients following CSWT. Reductions in creatine kinase (87.89 +/- 36.69 to 86.22 +/- 35.96 IU/L, P = 0.046), creatine kinase MB (10.89 +/- 5.73 to 10.11 +/- 5.93 IU/L, P = 0.008), aspartate transaminase (interquartile range [IQR] 28.00 to 27.00 IU/L, P = 0.034) were also found. Angina (Canadian Cardiovascular Society scale IQR 3.0 to 2.0, P = 0.035) and nitroglycerin dose reduction (IQR 3.0 to 1.0 times/wk, P = 0.038) were reported. Conclusions: This study is a preliminary assessment of CSWT in patients with refractory CAD. We report that CSWT is a noninvasive, effective, and safe intervention in the treatment of refractory CAD.