Despite the increasing use of alternative techniques, endomyocardial biopsy remains the primary method for diagnosing cardiac allograft rejection. Between March 1986 and May 1994, 2,894 endomyocardial biopsies performed on 183 heart transplant patients were reviewed. A total of 53 (1.8%) complications occurred. 33 (1.1%) complications were associated with the introduction, including carotid puncture (0.9%), neurological reaction (0.1%), and pneumothorax (0.1%). Complications during biopsy included arrhythmias (0.4%) and ventricular perforation (0.2%). In addition, we observed three episodes of allergic reaction to a reusable biotome, three episodes of liver biopsy, and one case of pacemaker dislodgement. All complications were without significant long-term sequelae. In contrast to the cardiomyopathy population, no severe ventricular perforations or deaths occurred. Thus although endomyocardial biopsy has some risk, it continues to be a safe and effective way of monitoring rejection.