Objectives: Osteoporosis is a major cause of morbidity in the elderly. Although acute kidney injury (AKI) due to active vitamin D3 analogs, one of its therapeutic drugs, is often encountered in clinical practice, epidemiological studies are scarce, with previous reports predominantly consisting of case reports and case series. This study aimed to clarify the association between AKI and active vitamin D3 analogs, and to identify the risk factors using the Japanese Adverse Drug Event Report (JADER) database, a nationwide spontaneous database on drug adverse effect. Methods: We extracted the adverse event reports suspected to be associated with insurance-covered active Vitamin D3 analogs for osteoporosis in Japan (eldecalcitol, alfacalcidol, and calcitriol) from April 2004 to September 2023. AKI was defined based on the preferred terminology by the Medical Dictionary for Regulatory Activities/Japanese (MedDRA/J) version 26.1. We calculated reporting odds ratio (RORs) and 95% confidence intervals (CIs) for each drug. We also identified the risk factors associated with AKI using multiple logistic regression analysis. Results: Among 298,891 reports of all adverse events in the analysis, 621, 408, and 42 reports implicated eldecalcitol, alfacalcidol, and calcitriol as suspect drugs, respectively. Among them, 236, 67, and 6 reports had AKI. There was a significant association of AKI with active vitamin D3 analogs (ROR [95% CI]: eldecalcitol 16.75 [14.23-19.72], P<0.001; alfacalcidol 5.28 [4.07-6.87], P<0.001; calcitriol, 4.46 [1.88-10.59], P<0.001). Multiple logistic regression analysis showed a significant association of AKI with age ≥70 years (Odds Ratio (OR) [95% CI], 1.52 [1.08-2.14]; P=0.016), weight <50 kg (1.65 [1.20-2.26]; P=0.002), hypertension (1.85 [1.39-2.47]; P<0.001), and the concomitant use of NSAIDs (1.66 [1.17-2.36], P=0.005). Conclusions: Our results suggest active D3 analogs may increase the risk of AKI. Particularly, when prescribing these drugs to patients with risk factors, careful consideration should be given to monitoring renal function.