<h4>Objective</h4>To investigate the associations of C-reactive protein (CRP), triglyceride-glucose (TyG) index, and their composite-the CRP-TyG index (CTI)-with sequential trajectories within the cardiovascular-renal-diabetes (CRD) cluster, including incident coronary artery disease (CAD), type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and multimorbidity.<h4>Methods</h4>We analyzed 333,698 participants from the UK Biobank who were free of CAD, T2DM, and CKD at baseline. Here, CRP is linked to type 2 diabetes mellitus.