This study examined consequences of gastrointestinal (GI) complications and mycophenolate mofetil (MMF) discontinuation on long-term outcomes in patients who received MMF at transplantation and had graft function 12 months post-transplantation. Data were obtained from the United States Renal Data System for cadaveric renal transplant recipients between 1995 and 1998. GI complications or MMF discontinuation occurred in 27.4% and 17.5% of patients, respectively. MMF was discontinued in 21.3% of patients with GI complications and 16.0% of patients without (P<0.00001). Four-year graft survival was reduced from 87.1% to 82.3% (P=0.091) with MMF discontinuation, to 83.0% (P=0.001) with GI complications, and to 70.2% (P<0.0001) with GI complications and MMF discontinuation. While the retrospective nature of this work cannot prove causality, which will require future prospective studies, both GI complications and MMF withdrawal are associated with increased risk of graft loss and may warrant further study in the management of transplant recipients.