Background: Blood transfusion has been shown to impact rejection after renal and cardiac transplantation, but it has not been studied after lung transplantation (LTx). In this study we assess: (1) patterns of transfusion, and (2) temporal interrelationships with histologic evidence of rejection. Methods: From July 1998 to January 2006, 326 of 331 patients undergoing LTx had available for study both time-related post-operative blood transfusion data and their series of transbronchial biopsy evaluations of perivascular rejection grade (Grades A0 to A4). Longitudinal temporal decomposition for ordinal variables was used to characterize prevalence of rejection grade and simultaneously assess the influence of (a) red blood cell (RBC), (b) platelet and (c) plasma administration. Results: Although peri-operative transfusion was common, transfusions continued at a low, steady rate throughout the life of LTx patients; patients received a total of 2,841 RBC units through follow-up. Immediately after LTx, the prevalence of Grade A0 rejection was 51%, and this increased to 84% by 6 months. RBC transfusion between biopsies was associated with lower histologic grade of rejection (70%, 73% and 77% with Grade A0 for 0, 1 and 12 units, respectively; p = 0.009), and this was particularly evident early after LTx. Histologic grade was not influenced by platelets or plasma. Conclusions: Transfusion requirements are high and continue throughout life after LTx; causes and effective treatment of persistent anemia should be sought. RBC transfusion appears to have an immunosuppressive effect, particularly early after transplant. J Heart Lung Transplant 2009;28: 558-63. Copyright (C) 2009 by the International Society for Heart and Lung Transplantation.