Long-term data on atrial fibrillation (AF) impact on tricuspid regurgitation (TR) progression and its relation to pulmonary pressure are scant. We investigated this association in a study spanning over a decade. Adults with echocardiographic evaluation before 2014, free of significant TR, were included. Patients were dichotomized by baseline AF, followed by stratification according to systolic pulmonary artery pressure (sPAP). The development of new significant TR and its impact on mortality were studied. Study population included 21502 patients (median age 65, 40% female), 13% had baseline AF. During a median follow-up of 12 years, 11% developed significant TR. Compared with patients free of AF, patients with baseline AF were 3.5 and 1.3 times more likely to develop significant TR in a univariate and multivariate models, respectively (95% CI 3.27-3.91, 1.18-1.44, p<0.001 for both). The risk of TR progression was higher in patients with permanent AF and those treated with rate control strategy (HR 1.95 and 2.01, respectively; p<0.001 for both). The association of AF with TR progression was sPAP-related, being more pronounced among patients with normal sPAP than among those with elevated sPAP (HR 1.5vs. 1.18; p for interaction<0.001). TR progression was independently linked to a two-fold higher mortality risk, consistent regardless of baseline AF (p<0.001). AF is an independent predictor of TR progression, especially in patients with normal sPAP. Subsequent research on strategies to prevent TR progression in this patient population are warranted.This analysis investigated the association of AF with TR progression, and the interaction of pulmonary arterial pressure with this link. Among patients with AF (Left), progression to significant TR is highly prevalent, with higher risk among patients with permanent AF and lower risk in those treated with rhythm control strategy. Pulmonary arterial pressure interacts with this association (Right), such that among patients with normal sPAP, the link between AF and TR progression is stronger, suggesting that the importance of proactive AF management in this sugroup of patients. TR has important implications on mortality, regardless of AF status (Middle).AF=Atrial Fibrillation; A-STR=Atrial Secondary TR; CIED=cardiac implantable electronic device; TR=Tricuspid Regurgitation; V-STR=Ventricular Secondary TR.