Renal allograft survival requires the administration of multiple immunosuppressive drugs. This strategy may lead to gastric complications that necessitate gastro-protective medications, notably, proton pump inhibitors (PPIs). This study aimed to compare the effects of pantoprazole and esomeprazole on renal function in stable renal transplant recipients. A prospective, parallel, open-label clinical trial was performed with forty-seven adult renal transplant recipients receiving immunosuppressive therapy with cyclosporine (CSA) doses adjusted to attain trough concentrations of 100-150 µg/L, mycophenolate mofetil (MMF) at 750 mg q12 hr and prednisolone at 5 mg daily at Nasser Institute, Cairo, Egypt. The enrolled participants were randomized into two groups, which received either esomeprazole or pantoprazole at the same dose (40 mg once daily). Renal function was measured at baseline and monthly for 6 months. The study was conducted between January-September 2016. Main outcome measures clinical signs of rejection reflected by renal function decline, assessed by elevated levels of serum creatinine. The mean serum creatinine level was significantly lower in the sixth month than at baseline in esomeprazole group (p 0.004); interestingly there was a continuous decrease of serum creatinine levels in esomeprazole group and nearly constant values in pantoprazole group. There was no significant difference in serum creatinine levels between the two groups. From this study, it could be concluded that esomeprazole may be preferred over pantoprazole in renal transplant recipients because it decreased serum creatinine which is one of the markers of chronic allograft rejection in stable renal transplantation recipients.