Many studies suggest that 1,25-dihydroxyvitamin D3 (1,25-[OH](2) D3) and its analogues are potent dose-reducing drugs for other immunomodulators, helping to prevent graft rejection. In this study, we retrospectively grouped renal transplant recipients into two cohorts based on 1,25-[OH](2) D3 use to analyze the immunomodulatory effects. Ninety-two subjects were initially enrolled: group A (n = 43) recipients who had osteoporosis and were treated with 1,25-[OH](2) D3, and group B (n = 49) was a control group. We evaluated the effects on the number of acute rejection episodes, the immunosuppressive drug doses, serum calcium levels, and overall graft survival. Although before treatment the number of acute rejection episodes was statistically higher among group A than group B patients, after introduction of 1,25-[OH](2) D3, the difference became nonsignificant. This study showed that osteoporotic renal transplant recipients experienced fewer acute rejection episodes after 1,25-[OH](2) D3 treatment.