Background: Although the Cylex immune assay has been proposed as a means of tailoring immunosuppression after organ transplantation, there are limited data regarding its utility in cardiac transplant recipients. Therefore, we sought to determine the utility of the Cylex assay in assessing the risk of infection or rejection in cardiac transplant recipients. Methods: This study is a retrospective review of the clinical course of all adult cardiac transplant recipients who underwent a Cylex assay at UT Southwestern Medical Center between January 2004 and September 2007. Results: One hundred eleven patients were free of significant rejection or infection at the time of the first Cylex assay. Most patients (92%) were >1 year post-transplant. Over the next 157 ± 41 (mean ± SD) days, 2 patients had 3 episodes of rejection requiring therapy and 7 patients had 8 infections requiring therapy. The Cylex responses ranged from 17 to 894 ng/ml. No correlation was observed between the baseline Cylex response and subsequent risk of either infection or rejection within 6 months. Lower white blood cell count and African American ethnicity were correlated with a lower Cylex response. Conclusions: In this study, the Cylex assay had limited utility as an adjunct to routine clinical evaluation in assessing risk of infection or rejection in cardiac transplant recipients.