The inter-arm blood pressure difference has been advocated to be associated with cardiovascular mortality and morbidity. Our study aimed to investigate the association between Inter-arm systolic and diastolic blood pressure differences and Cardio Vascular Disease (CVD). A total of 10,126 participants aged 35–70 years old were enrolled in a prospective Fasa Persian Adult Cohort. In this cross-sectional study, the cutoff values for inter-arm blood pressure difference were less than 5, greater than 5, greater than 10, and greater than 15 mm Hg. Descriptive statistics and logistic regression were used to analyze the data. Based on the results the prevalence of ≥ 15 mmHg inter-arm systolic and diastole blood pressure difference (inter-arm SBPD and inter-arm DBPD) were 8.08% and 2.61%. The results of logistic regression analysis showed that inter-arm SBPD ≥ 15 and (OR<5/≥15= 1.412; 95%CI = 1.099–1.814) and inter-arm DBPD ≥ 10 (OR<5/≥10= 1.518; 95%CI = 1.238–1.862) affected the risk of CVD. The results showed that the differences in BP between the arms had a strong positive relationship with CVD. Therefore, inter-arm blood pressure could be considered a marker for the prevention and diagnosis of CVD for physicians.