Background and objective Prevention of atherosclerotic cardiovascular diseases (ASCVD) is possible with early recognition of individuals at risk. Salusin alpha is an endogenous bioactive peptide with anti-atherogenic properties. We aimed to reveal the relationship between salusin alpha levels and cardiovascular (CV) risk using the Systematic COronary Risk Estimation 2 (SCORE2) and Pooled Cohort Equation (PCE) algorithms. Methods A total of 137 asymptomatic outpatients were included in the study. The participants were divided into four quartile groups according to the distribution of salusin alpha levels: Q1 (n = 34), Q2 (n = 35), Q3 (n = 34), and Q4 (n = 34). The relationships of salusin alpha with cardiovascular risk scores and groups were investigated. Results The means of SCORE2 and PCE risk scores (11.24 ± 1.24 and 13.30 ± 1.71, respectively; p < 0.001 for both), baseline scores in the presence of SCORE2 and PCE optimal risk factors (4.82 ± 0.71 (p = 0.034); 4.20 ± 0.77 (p = 0.010)), and means of Δ SCORE2 and Δ PCE risk score (6.41 ± 0.67 and 9.10 ± 1.10, respectively; p < 0.001 for both) were significantly higher in the Q1 group. The SCORE2 "very high"cardiovascular (CV)risk group was significantly represented in the Q1 group (n = 17 (50%)), while the "low-moderate" risk group was more heavily represented in the Q4 group (n = 15 (44.1%)) (p < 0.001). The PCE"high"CV risk group was significantly represented in the Q1 group (n = 9 (26.5%)), while the "low" risk group was more intensely represented in the Q4 group (n = 20 (58.8%)) (p < 0.001). Salusin alpha had a significantly negative moderate correlation with SCORE2 and PCE risk scores. As a result of receiver operating characteristic (ROC) analysis, it was found that salusin alpha had significant diagnostic power in the prediction of CV risk groups determined by SCORE2 and PCE risk scores. Salusin alpha was observed to be a risk-reducing factor in SCORE2 and PCE CV risk groups (odds ratio (OR)(95% confidence interval (CI)): 0.989 (0.982-0.997) (p = 0.002) and OR (95% CI): 0.988 (0.978-0.998) (p = 0.009) respectively). Conclusion Salusin alpha has a negative correlation with SCORE2 and PCE risk scores. It has significant diagnostic power in the prediction of CV risk groups and is an independent variable that has a risk-reducing effect in the distribution of risk groups.