Background: YKL-40 (human cartilage glycoprotein 39, chitinase-3-like protein 1) is an inflammatory marker secreted mainly by macrophages and has distinctive roles on extracellular matrix remodeling, macrophage maturation, adhesion, and migration. Despite the presence of robust data suggesting the association of YKL-40 with variety of cardiovascular diseases (CV), there is no study up to date evaluating the role of YKL-40 on the long-term prognosis in patients with hypertension (HT). Methods: A single center, prospective, observational cohort study that included 327 consecutive hypertensive patients which were presented to a cardiology outpatient clinic. Patients were followed up for 7.89 +/- 0.12 years. Primary outcome of the study was the occurrence of major cardiovascular outcomes (MACE) defined as all-cause mortality, new onset heart failure (HF), and coronary artery disease (CAD) requiring revascularization. Results: A total of 135 patients constituted the final study population [mean age: 52.4 +/- 10.2, female: 63 (46%)]. A total of 28 (20.7%) patients had MACE during the follow up. Cox regression analysis revealed that age (HR: 1.046, 1.016-1.093 CI 95%, p = .026), diabetes (HR: 2.278, 1.026-5.057 CI 95%, p = .043), and YKL-40 level (HR: 1.019, 1.013-1.026 CI 95%, p = .005) significantly predicted MACE. We found that sensitivity and specificity of YKL-40 > 93.5 for predicting MACE was 71.4% and 65%, respectively with an area under curve (AUC) 0.723 (0.617-0.828 CI 95%, p < .001) Conclusion: Elevated serum YKL-40 level predicted MACE in hypertensive patients during a long-term follow up.