Introduction Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the presence of somatic mutations in hematopoietic stem cells of individuals without apparent blood disorders. Inflammatory processes may contribute to CHIP, creating a vicious cycle that puts afflicted individuals at increased risk for systemic illnesses, including hematologic malignancies, thrombotic disorders, and cardiovascular diseases, among others. JAK2V617F, one of the key mutated driver genes in myeloproliferative neoplasms (MPNs) and commonly observed in CHIP, is a well-known risk factor of thromboembolism in MPNs. However, the association between JAK2-CHIP and microthromboembolism-related events (miTE-REs) in the general population is not well understood, which is the focus of this study. Method A retrospective cohort of 1,768 participants from a health screening population, who visited our affiliate for annual health exams and had stored blood samples, was included in this study. Their longitudinal medical records were examined to identify the development of diseases of interest. The miTE-REs defined in this study included neurological disorders (dementia, Parkinsonism, and Alzheimer's disease {AD}) in the absence of cerebral vascular events, congestive heart failure (CHF) in the absence of ischemic heart disease, and avascular necrosis (AVN) of the femoral head. JAK2V617F was quantitatively detected in peripheral blood granulocytes using the qCAST-Duplex PCR method, with a detection limit of mutant allele burden (AB) set at 0.1% as described previously [Hsu, C.C. et al. Haematologica 2018, 103, e450-e454]. Results JAK2-CHIP was identified in 32 (1.8%) of the total population. Its prevalence was significantly higher in individuals aged 70 years or older (2.51%) compared to those younger than 70 (1.37%, p=0.03). The mean age of JAK2-CHIP carriers was significantly higher than that of non-carriers (68.3 ± 11.6 vs. 63.2 ± 14.0, p=0.044). There were no significant differences in the prevalence of diabetes, hypertension, hyperlipidemia, and gout between the two groups. JAK2-CHIP carriers were more likely to develop Parkinsonism (15.6% vs. 6.3%, p=0.035). However, there were no significant differences in the incidences of dementia, AD, CHF, and AVN between JAK2-CHIP carriers and non-carriers. None of the JAK2-CHIP carriers had more than one miTE-RE. Most hematological parameters and lipid profiles were similar across the groups, except for a higher platelet count observed in the JAK2V617F AB ≥ 1% subgroup compared to the JAK2(-) group (313 ± 61 vs. 223 ± 65 x 10^9/L, p=0.004). Among 22 JAK2-CHIP carriers with serial blood samples, 5 showed increased JAK2 AB over time, including 2 with an initial AB < 1%. Conclusion This study highlights that JAK2-CHIP carriers are older than their JAK2(-) counterparts and have similar comorbidity profiles. JAK2-CHIP presence is associated with a higher risk of Parkinsonism but not other miTE-REs, whereas a notably higher platelet count is observed in those with a higher JAK2 AB. These findings suggest that the significance of JAK2-CHIP might warrant further investigation to better understand its clinical implications.