Background: Abnormal kidney function is one of the risk factors for cardiovascular diseases. Whether the association between a wide range of kidney functions from normal to advanced chronic kidney disease and stroke risk is unclear. Methods: A cross-sectional study involving participants (≥ 18 years old) in the 2017 - 2020 NHANES was examined for the association between serum creatinine (SCr) and history of stroke informed by a doctor or other health professional by multiple logistic regression analysis. Results: Of 9,211 participants, the mean±SD age was 51±18 y/o and 52% were female. White accounts for 35% followed by Black (27%), Asian (12%), Mexican American (11%), Hispanic (10%), and others (5%). Up to 485 participants (5%) ever had a stroke. Median (IQR) SCr was 0.84 (0.71 - 1.01) mg/dL. Stratified SCr among 7,865 participants with SCr data into quartile (Q), mean SCr were 0.62, 0.78, 0.92, and 1.34 mg/dL, respectively (Figure 1A). Compared to participants in Q1, strokes were 1.72 and 3.45 times as likely to occur in those in Q3 and Q4, respectively (Q3: 95%CI 1.24, 2.39, P 0.001; Q4: 95%CI 2.55, 4.67, P <0.0001); while participants in Q2 were 1.41 times as likely to have strokes but not statically significant (95%CI 0.99, 2.00, P 0.055; Figure 1B). After adjusting for age, gender, race, BMI, only participants in Q4 were 1.64 times as likely to have a stroke compared to those in Q1 (95%CI 1.09, 2.45, P 0.017); while strokes were 1.158 and 1.21 times as likely to occur among participants in Q2 and Q3, respectively but not statically significant (Q2: 95%CI 0.78, 1.72, P 0.468; Q3: 0.81, 1.80, P 0.348). There were effect modifications between SCr in Q4 and some races (Hispanic, White, and others; P interaction 0.04, 0.013, and 0.011, respectively). Conclusions: SCr was positively associated with the likelihood to have a stroke. Longitudinal cohort studies are required to further elucidate the relationship.