Objectives: Follistatin-like protein-1 (FSTL-1) is cardiokine which are involved in the induction of angiogenesis, stimulation of cardiomyocyte proliferation and inhibition of hypertrophy. While FSTL-1 is a noticeable therapeutic target of several cardiovascular (CV) disease, the clinical significance of circulating FSTL-1 levels remains unclear in hemodialysis patients. Methods: A total 281 HD patients from the K-cohort were prospectively enrolled from June 2016 to March 2020. Plasma FSTL-1 level and echocardiographic findings at baseline were examined. The primary endpoint was defined as a composite of CV events and death.   Results: Plasma FSTL-1 level showed weakly positive correlation with E/A and E/E’ ratio. However, left ventricular (LV) mass index, LV dimension, LV volume and LV ejection fraction were not correlated. The cumulative event rate of the composite of CV event and death was significantly greater in FSTL-1 tertile 3 (p = 0.048). In multivariative Cox regression analysis, FSTL-1 tertile 3 was associated with a 2.48-fold risk for the composite of CV events and death (95% confidence interval [CI], 1.34–4.60), a 2.77-fold risk for CV events (95% CI, 1.30–5.91) and a 2.36-fold risk for cardiac events. Conclusions: Plasma FSTL-1 levels were not correlated with cardiac hypertrophy and morphology, but higher FSTL-1 levels increased the risk of CV and cardiac events in HD patients, suggesting that deeper involvement of FSTL-1 in incident CV pathology than in current cardiac remodeling.