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Abstract Background Hemoglobin levels fluctuate in patients on hemodialysis, and a rapid increase in hemoglobin may trigger thromboembolism. However, the association between annual variability in hemoglobin levels and thromboembolism in patients on hemodialysis remains unclear. Methods This multicenter, retrospective cohort study included 307 patients (202 males) who underwent continuous hemodialysis at one of the three Shibagaki Clinics (Jiyugaoka, Togoshi, and Kugahara) from April 2019 to March 2020. The mean age was 70.0 ± 12.5 years, and the median hemodialysis duration was 5.1 years. Annual hemoglobin variability was defined as the standard deviation of hemoglobin levels, calculated from monthly predialysis hemoglobin values over a 1-year period. During the observation period from April 2020 to March 2023, the primary outcome was the association between hemoglobin variability and the incidence of thromboembolism (acute coronary syndrome, cerebral infarction, and vascular access thrombosis), and the secondary outcomes were major adverse cardiovascular events (MACEs) and all-cause hospitalization, evaluated using the Cox regression analysis. Results The mean annual hemoglobin variability was 0.76 ± 0.32 g/dL. Patients were classified into three groups on the basis of hemoglobin standard deviation tertiles. By log-rank test, the patients with high hemoglobin variability had significantly lower rates of thromboembolism-free survival ( P < 0.001) and all-cause hospitalization-free survival ( P = 0.034), compared with those with low hemoglobin variability. By Cox regression analysis adjusted for age, sex, hemodialysis duration, comorbidities, mean annual hemoglobin level, and other dialysis-related parameters, greater hemoglobin variability was significantly associated with a higher risk of thromboembolism (hazard ratio [HR], 3.84; 95% confidence interval [CI], 2.03–7.28, P < 0.001), MACEs (HR, 1.92; 95% CI 1.02–3.61; P = 0.044), and all-cause hospitalization (HR, 1.64; 95% CI 1.08–2.50; P = 0.022). Sensitivity analysis using the subdistribution hazard model yielded results similar to those observed for the primary outcome (subdistribution HR, 4.70; 95% CI 2.50–8.83; P < 0.001). Conclusions In Japanese patients on hemodialysis, a greater mean annual hemoglobin variability was associated with thromboembolism, MACEs, and all-cause hospitalization. Further studies are warranted to investigate whether reducing annual hemoglobin variability can aid in mitigating thromboembolic events in patients on hemodialysis.