Medical comorbidities (CM) contribute to cardiac rehabilitation (CR) underutilization. Whether individuals with coronary heart disease and an increased CM burden achieve similar benefits from CR as those with a low CM burden is unknown. We analyzed 794 patients with coronary heart disease completing CR from 1/96 to 4/08. Medical CM burden was assessed using a comorbidity index (CMI) previously validated in a CR population. Distance achieved on a 6-minute walk test, body mass index, and the physical and mental component scores on the Medical Outcomes Short Form 36 were measured at baseline and at CR completion. We performed multivariable linear regression to compare changes in these parameters between individuals with a low CM burden (CMI = 0) and those with a moderate (CMI = 1-2) or high (CMI > 2) CM burden by age group (<56, 56-65, and >65 years of age). Mean age was 61.6 ± 10.6 years, 29% were women, 31% nonwhite; 305 individuals had a CMI = 0, 305 had a CMI = 1 to 2, and 184 had a CMI > 2. All subgroups, regardless of age or CMI, demonstrated improvements with CR on virtually all parameters measured. Among individuals younger than 56 years, those with a CMI = 0 had greater improvements in these parameters after multivariable adjustment than those with a CMI of 1 to 2 or more than 2. In contrast, in older age groups, the degree of improvement was similar regardless of CMI. All patient groups, regardless of CM burden, benefited from CR. Medical CM burden, especially among older patients, should not discourage referral to CR.