ABSTRACT Introduction Atorvastatin, one of the most widely used drugs, has attracted controversy regarding its potential adverse reactions to acute kidney injury(AKI). This study aims to provide evidence in support of the safe use of atorvastatin. Areas Covered Using the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q1 2024), we extracted reports where atorvastatin was the primary suspect and categorized them into five populations: the general population, acute myocardial infarction (AMI), ischemic stroke (IS), type 2 diabetes mellitus (T2DM), and hyperlipidemia (HLD). We performed subgroup analyses by gender and age strata within these populations, assessing positive signals through disproportionality analysis using four criteria: Ratio of Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EGBM). The statistical analysis evaluated differences between adverse drug reaction (ADR) occurrence and nonoccurrence, as well as between high and low induction time groups. Expert Opinion In the general population, evidence for a positive signal of AKI was insufficient. However, the sub-group analysis revealed a risk in males, with older individuals more often affected in both AMI and IS populations. In T2DM, positive signals were evident in younger age groups. For the HLD population, evidence of a positive AKI signal was insufficient across gender and age strata. Overall, atorvastatin is generally safe, but clinical vigilance for AKI is warranted in T2DM, AMI, and IS populations, particularly in older adults (65+ years).