Active vitamin D₃ (VDRAs) can cause drug-induced hypercalcemia and acute renal failure. Eldecalcitol (ELD), a VDRA, promotes bone formation more strongly than other VDRAs, such as alfacalcidol (ALF), but whether or not ELD affects serum calcium (Ca) levels and renal function more significantly than other VDRAs is unclear. In Japan, the supply of ALF was temporarily stopped in 2021, and patients at Fukuoka University Hospital who were taking ALF were either switched to ELD or discontinued ALF. We retrospectively investigated how these prescription changes affected serum Ca levels and renal function. Sixty-seven adult patients who were admitted to our hospital for at least 5 d between September 2021 and March 2022 and were taking ALF at the time of admission were divided into 3 groups: 36 patients who continued ALF (ALF-C), 12 who were switched to ELD (ELD-S), and 19 who discontinued VDRAs (DC). The changes in weekly serum Ca levels and renal function during hospitalization were compared between the groups. At the second week of observation, the change in the serum Ca level was 0.01 mg/dL in the ALF-C group, +0.45 mg/dL in the ELD-S group, and −0.37 mg/dL in the DC group, showing a significant difference among these groups. In addition, serum Ca levels were increased in all patients in the ELD-S group at Week 2. The estimated glomerular filtration rate didn’t change significantly in any group during hospitalization. These results suggest that serum Ca levels should be measured by Week 2 when ELD is newly started or changed.