Objectives. This study was designed to determine the risk of performing percutaneous transluminal coronary angioplasty (PTCA) at the time of diagnostic catheterization ('combined procedures'). Background. Health care providers are under increasing pressure to combine diagnostic and interventional coronary procedures to reduce costs. However, the risk associated with combined procedures has not been rigorously assessed. Methods. A multicenter cohort study of 35,700 patients undergoing elective PTCA from 1992 through 1995 was performed to determine the risk of major complications (myocardial infarction, emergency coronary artery bypass graft surgery or death) from combined relative to staged procedures (i.e., performing PTCA at a session subsequent to diagnostic catheterization). Results. The risks of major complications from combined and staged procedures were 2.0% and 1.6%, respectively (unadjusted odds ratio [OR] 1.28, 95% confidence interval [CI] 1.05 to 1.57). After adjusting for clinical and angiographic differences and clustering by laboratory, the risk from combined procedures was not significantly elevated (multivariable OR 1.18, 95% CI 0.89 to 1.55). However, several subgroups of patients did have an increased risk from combined procedures: patients with multivessel disease (multivariable OR 1.64, 95% CI 1.13 to 2.39); women (multivariable OR 1.64, 95% CI 1.05 to 2.55); patients >65 years old (multivariable OR 1.40, 95% CI 1.02 to 1.93); and patients undergoing multilesion PTCA (multivariable OR 1.53, 95% CI 1.06 to 2.21). The risk of combined relative to staged procedures decreased over the 4-year period (multivariable p = 0.029). Conclusions. Combining PTCA with diagnostic catheterization appears to be safe in many patients. However, several subgroups of patients may be at increased risk. Careful patient selection will most likely remain critical to ensuring the safety of combined procedures.