*Purpose: To determine if there is a difference in 90 day Clostridium difficile infection (CDI) rates before and after the stress ulcer prophylaxis (SUP) protocol change from proton pump inhibitors (PPIs) to histamine-2-receptor antagonists (H2RAs) following liver transplantation.

*Methods: This single-institution retrospective study included adult patients who underwent liver transplantation between 2014 and 2017, before and after a protocol change from PPI to H2RA as the preferred agent for SUP. Multi-organ transplant recipients were excluded. The PPI protocol group included patients transplanted before protocol change and the H2RA protocol group included patients transplanted after protocol change. The primary endpoint compared the 90 day incidence of CDI between groups. Secondary endpoints compared the 90 day incidence of gastrointestinal bleeding (GIB), pneumonia, biopsy proven rejection, and hypomagnesemia between the groups.

*Results: Three hundred and four patients were reviewed and 294 patients were included (147 in both PPI and H2RA protocol groups). Demographics were similar in both groups. Most recipients were caucasian males with a median age of 60 years. Model for end-stage liver disease (MELD) and incidence of peptic ulcer disease at the time of transplant were statistically higher in H2RA protocol group. The 90 day CDI rates in the PPI and H2RA protocol groups were not statistically different at 8.2% and 5.4% respectively (P=0.488). There was also no statistical difference in the 90 day incidence of GIB (5.4% versus 10.2%; P=0.192), pneumonia (9.5% versus 12.2%; P=0.575), and biopsy proven rejection (1.4% versus 5.4%; P=0.103) in the PPI and H2RA protocol groups respectively. There was a significantly higher 90 day incidence of hypomagnesemia in the H2RA protocol group compared to the PPI protocol group (42.9% versus 57.1%; P=0.020).

*Conclusions: There was no statistically significant difference in CDI rates between PPI and H2RA protocol groups. SUP protocol change from PPI to H2RA did not result in any difference in GIB, pneumonia, or biopsy proven rejection. The increased incidence of hypomagnesemia was statistically higher in the H2RA protocol group. In summary, H2RA SUP prophylaxis appears to be safe and effective following liver transplantation.

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