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Objectives: Prophylactic acid suppression with proton pump inhibitors or H2 receptor antagonists is often administered after kidney transplantation. The association of proton pump inhibitors or H2 receptor antagonists with acute rejection, hypomagnesemia, and graft loss in kidney transplant recipients is not well established. Materials and Methods: We performed a retrospective cohort study of 302 kidney transplant recipients at one center (57% male; mean age 35.5±11.2 years) with more than six months post-transplant follow-up. Recipients were grouped according to gastric acid prophylaxis: only proton pump inhibitors (n=179), only H2 receptor antagonists (n=42), proton pump inhibitors and H2 receptor antagonists (n=55), and nonusers (n=26). The primary outcome was biopsy-proven acute rejection. Graft loss and hypomagnesemia were defined as secondary outcomes. Results: Nonusers were younger and mostly under steroid-free immunosuppression compared to other study groups (p = 0.030 and p = 0.009, respectively). The primary outcome was similar across study groups (p = 0.266). Kaplan-Meier analyses also demonstrated similar 10-year graft survival rates: 95.5% for proton pump inhibitors, 97.6% for H2 receptor antagonists, 100% for proton pump inhibitors/ H2 receptor antagonists, and 96.2% for nonusers (p = 0.275). Conclusions: Using proton pump inhibitors is not associated with acute rejection or graft loss but may cause mild hypomagnesemia in kidney transplant recipients. [ABSTRACT FROM AUTHOR]