Over the past decade, the frequency of use of enhanced external counterpulsation (EECP®) has increased in patients with angina, irrespective of medical therapy and coronary revascularization status. Many patients referred for EECP® have one or more comorbidities that could affect this treatment's efficacy, safety, or both. By use of data from more than 8,000 patients enrolled in the International EECP® Patient Registry, we provide practical guidelines for the selection and treatment of patients. We have focused on considerations for patients who have one or more of the following characteristics: age older than 75 years, diabetes, obesity, heart failure, and peripheral vascular disease. We have also reviewed outcomes and treatment recommendations for individuals with poor diastolic augmentation during treatment, for those with atrial fibrillation or pacemakers, and for those receiving anticoagulation therapy. Lastly, we examined relevant data regarding extended courses of EECP®, repeat therapy, or both. While clinical studies have demonstrated the usefulness of EECP® in selected patients, these guidelines permit recommendations for the extended application of this important treatment to subsets of patients excluded from clinical trials.