Biomarker-based preventative and monitoring strategies are increasingly used for risk stratification in cardiovascular (CV) disease. The aim of this study was to investigate the utility of longitudinal change in B-type natriuretic peptide (BNP) and sST2 concentrations for predicting incident major adverse CV events (MACE) (heart failure, myocardial infarction, arrhythmia, stroke/transient ischaemic attack and CV death) in asymptomatic community-based patients with risk factors but without prevalent MACE at enrolment. The study population consisted of 282 patients selected from the longitudinal STOP-HF study of asymptomatic patients with risk factors for development of MACE. Fifty-two of these patients developed a MACE. The study was run in two phases comprising of an initial investigative cohort (n = 195), and a subsequent 2:1 (No MACE: MACE) propensity matched verification cohort (n = 87). BNP and sST2 were quantified in all patients at two time points a median of 2.5 years apart. Results highlighted that longitudinal change in sST2 was a statistically significant predictor of incident MACE, (AUC 0.60). A one-unit increment in sST2 change from baseline to follow up corresponded to approximately 7.99% increase in the rate of one or more incident MACE, independent of the baseline or follow-up concentration. In contrast, longitudinal change value of BNP was not associated with MACE. In conclusion, longitudinal change in sST2 but not BNP was associated with incident MACE in asymptomatic, initially event-free patients in the community. Further work is required to evaluate the clinical utility of change in sST2 in risk prediction and event monitoring in this setting.© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.