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We sought to characterize the association between long-term changes in the N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) and changes in left ventricular (LV) structure and function in patients with stable coronary artery disease.We included 593 participants without significant valvular disease enrolled in the Heart and Soul Study. We evaluated the association of 5-year change in NT-proBNP (ΔNT-proBNP) with changes in echocardiography-determined LV ejection fraction (LVEF), LV systolic dysfunction (LVSD; LVEF < 50%), LV mass index, incident LV hypertrophy (LVH) (LV mass index >102 g/m2 for men and >88 g/m2 for women), and LV diastolic dysfunction (LVDD) using linear and logistic regression.Over 5 years, the prevalence of LVH declined from 36 to 32% (P < 0.001), the prevalence of LVDD increased from 11 to 14% (P = 0.035), mean LVEF decreased from 63 ± 9% to 62 ± 10% (P = 0.07), and the prevalence of LVSD increased from 9 to 11% (P = 0.12). Compared with the lowest ΔNT-proBNP quartile (≥8 ng/l decrease) the highest quartile (>218 ng/l increase) had significantly more incident LVH and LVSD (P < 0.001 for both), with a trend toward increased incidence of LVDD. In logistic regression models adjusted for demographics, cardiac comorbidities, baseline LV structure and function, medication use, kidney function, and baseline NT-proBNP, log-transformed ΔNT-proBNP was associated only with incident LVSD (odds ratio 2.48 × 106, 95% confidence interval 224.53–2.73 × 1010, P = 0.002).A ΔNT-proBNP is independently associated with incident LVSD in patients with stable coronary artery disease. This suggests that a long-term rise in NT-proBNP levels may warrant evaluation for incident LVEF less than 50%.