The effect of alcohol consumption on atrial fibrillation risk remains controversial. Evaluating the association of alcohol consumption with atrial fibrillation-related biomarkers may help better understand the relevant mechanistic underpinnings. We studied participants from the PREDIMED-Plus study, a weight-loss randomised trial in metabolically unhealthy adults. N-terminal pro-B-type natriuretic protein, high-sensitivity troponin-T (hsTnT), high-sensitivity C-reactive protein (hsCRP), 3-nitrotyrosine and procollagen type 1 carboxy-terminal propeptide were measured in serum at baseline and years 3 and 5 of follow-up. We calculated average alcohol consumption in drinks/d (1 drink = 14 grams alcohol) with validated FFQ. Using multivariable models, we estimated cross-sectional and longitudinal associations of alcohol consumption with log-transformed biomarkers. Among 523 participants (mean age (sd): 65·1 (4·9) years, 40 % female), mean alcohol consumption was 1 drink/d. Cross-sectionally, alcohol consumption was not associated with cardiac biomarkers. Longitudinally, compared with non-consumers, heavy drinkers at baseline (≥ 4 drinks/d) had smaller increases in hsTnT (β: −0·10, 95 % CI: −0·20, 0·00) over 5 years. In contrast, those who increased alcohol consumption over follow-up experienced greater increases in hsCRP (β: 0·31, 95 % CI: 0·00, 0·63) compared with those whose drinking behaviour stayed the same. In this high-risk population, higher baseline alcohol intake was associated with smaller increases in hsTnT over follow-up while increases in alcohol intake over time were associated with higher levels of systemic inflammation. These findings highlight the importance of considering longitudinal changes in average alcohol exposure when evaluating its relationship with cardiometabolic biomarkers.