Despite the increasing use of alternative techniques, endomyocardial biopsy remains the primary method for diagnosing cardiac allograft rejection. Improved patient longevity and an increasing number of transplantation centers are resulting in an increase in the number of biopsies performed. Although endomyocardial biopsy is usually considered a safe procedure, no large studies of the risks of endomyocardial biopsy specifically in the transplant population have been undertaken. To determine the risk of endomyocardial biopsy in these patients, we reviewed 2454 endomyocardial biopsies performed from January 1983 to December 1990 in 133 cardiac allograft patients at our institution. At the time of each endomyocardial biopsy, a worksheet was completed detailing the patient's interval history, the site of vascular introduction, the number of attempts, the number of specimens, and any complications encountered. A total of 74 (3.0%) complications occurred. Fifty-six (2.3%) complications were associated with catheter insertion, including carotid puncture (1.8%), vasovagal reaction (0.1%), and prolonged bleeding (0.4%). Complications during biopsy included arrhythmias (0.25%) and conduction abnormalities (0.2%). In addition, we observed five episodes (three patients) of allergic reaction to a reusable bioptome and one case of pacemaker dislodgement. All complications were without significant long-term sequelae. In contrast to the cardiomyopathy population, no ventricular perforations or deaths occurred. Thus although endomyocardial biopsy has some risk, it continues to be a safe and effective way of monitoring rejection.