Introduction: Vitamin D deficiency (25(OH)D <30 ng/mL) in renal transplant recipients (RTRs) is a frequent finding and represents an important component in the pathogenesis of secondary hyperparathyroidism (SHPT). Therefore, its more systematic supplementation is recommended. We herein report our experience on the impact of cholecalciferol supplementation on PTH and 25(OH)D levels in a group of RTRs with 25(OH)D <30 ng/mL and SHPT. Patients and Methods: For this purpose, 52 RTRs with SHPT were treated with cholecalciferol at the fixed dose of 25,000 IU p.o. weekly for 12 months. For the control group we selected 23 RTRs with SHPT and 25(OH)D levels <30 ng/mL. Every 6 weeks eGFR, sCa and sPO4 levels were evaluated; PTH, 25(OH)D, FECa e TmPO 4 were evaluated every 6 months. Results: At baseline, the two groups had similar clinical characteristics and biohumoral parameters. Parathormone was negatively correlated with 25(OH)D levels (r=-0.250; P <0.001) and TmPO4 values (r=-0.425; P<0.0001). At F-U there was a significant reduction in PTH levels in the supplemented group, from 131 ± 46 to 103 ± 42 pg/mL (P<0.001), while vitamin D levels, TmPO4 values, PO4 and sCa levels increased significantly, from 14.9 ± 6.5 to 37.9 ± 13.1 ng/mL (P<0.001), from 1.9 ± 0.7 to 2.6 ± 0.7 mg/dL (P<0.001), from 3.1 ± 0.5 to 3.5 ± 0.5 mg/dL (P<0.001), and from 9.3 ± 0.5 to 9.6 ± 0.4 (P<0.01), respectively. During the study there were no episodes of hypercalcaemia and/or hypercalciuria, while 25(OH)D levels always remained <100 ng/mL. In the control group, at F-U, PTH levels increased from 132 ± 49 to 169 ± 66 pg/ml (P <0.05), while 25(OH)D levels remained stable at <30 ng/mL. Conclusions: Vitamin D deficiency in RTRs is very frequent. Cholecalciferol supplementation is associated with a better control of SHPT and a correction of vitamin D deficiency in most patients, representing an effective, safe and inexpensive therapeutic approach to IPS.