OBJECTIVES: Mycophenolate mofetil (MMF) has been associated with increased risk of gastrointestinal (GI) complications in transplant recipients. Our aim was to assess the risk of GI medication use in heart transplant patients receiving MMF and their healthcare costs over a two-year period. METHODS: US commercial claims data for 233 patients receiving heart transplants between 1995 and 2005 were linked to data from the Organ Procurement Transplant Network. Patients were placed into two groups: received MMF (MMF group) and did not(non-MMF group). MMF recipients were identified as having =1 pharmacy claim post-transplant for MMF. For the MMF group, use of GI medications was defined as having =1 prescription (H2 antagonists, proton pump inhibitors, and miscellaneous GI agents) during the year following the initial claim for MMF. For those in the non-MMF group, the commensurate 1-year period post-transplant in which the GI claim occurred was defined based on the median time to the first MMF claim of the MMF group. A multivariate logistic regression and a Wilcoxon test were employed to assess risk of GI medication use and total medical costs 1 year before and after occurrence of GI medication claim, respectively. RESULTS: MMF was received by 173 (74%) patients. GI medication use occurred in 139 (80%) of the patients in the MMF group and in 29 (48%) of the patients in the non-MMF group. Patients who received MMF were associated with a statistically significant increase in risk of GI medication use compared to patients who did not receive MMF (OR=7.65, p<.0001). Patients using GI medications generated significantly greater costs compared to patients not using GI medications ($69,328 vs $48,301, p<.0001). CONCLUSION: Heart transplant recipients who receive MMF had 7.7 times greater risk of using GI medications compared to those who did not receive MMF, which leads to increased costs.