<p>In clinical states of relative aldosterone excess, such as in patients with chronic kidney disease (CKD), blockade of the overactivated mineralocorticoid receptor (MR) is a mechanistically plausible target of therapy in order to improve long-term cardiovascular and kidney outcomes. However, in the recently completed Benefits of Aldosterone Receptor Antagonism in Chronic Kidney Disease (BARACK-D) trial, the addition of spironolactone to standard care was not superior to standard care alone in improving cardiovascular outcomes in high-risk patients with moderate CKD. The use of spironolactone over the course of the BARACK-D trial was commonly restricted by hyperkalemia and other side effects. In sharp contrast, finerenone is a novel, selective, non-steroidal MR antagonist with proven cardiorenal protective effects and a more favorable side-effect profile. In a prespecified, individual patient-level data synthesis of 3 large clinical trials, as compared with placebo, finerenone significantly reduced the risks of all-cause death, hospitalization for heart failure and progression of CKD in a broad spectrum of patients with cardio-kidney-metabolic diseases. Although the risk of hyperkalemia with finerenone is real, the permanent discontinuation of treatment due to hyperkalemia occurs rarely. Accordingly, finerenone appears to be a safer therapeutic option with well-documented benefits on cardiovascular and kidney outcomes. In this article, we provide a comparative evaluation of safety and efficacy of spironolactone with that of finerenone. We discuss differences in pharmacodynamic and pharmacokinetic properties as well as data for the safety and efficacy of these 2 MR antagonists. We conclude with a call for a trial aiming to provide a direct and head-to-head comparison between spironolactone and finerenone in high-risk patients with cardio-kidney-metabolic diseases in the future.</p>