Background and objective: Prolonged standing is one of the significant contributors to chronic venous insufficiency (CVI) in industry workers. Yoga is proven to be an effective therapy in treating occupational hazards. The current study aimed to investigate the effect of yoga on CVI among industry workers. Methodology: Male workers ( n = 100) from machinery manufacturing industries in Bangalore meeting the inclusion and exclusion criteria were recruited for the study. The yoga group received a specifically designed yoga module for 6 days a week for 12 weeks, and the control group was offered lifestyle suggestions. Plasma homocysteine was used as the primary outcome variable, whereas Venous Clinical Severity Score, ankle brachial pressure index (ABPI), ankle and calf circumference, CVI questionnaire, and Chalder fatigue scale were assessed as secondary variables at baseline and the end of 12 weeks of intervention. Results: Eighty-eight participants (yoga = 43, control = 45) completed the study. A one-way analysis of covariates (ANCOVA) was used to determine the significant differences between groups in the post-values. A significant difference was found between groups in plasma homocysteine (partial eta squared = 0.34, p < 0.001). All variables, except for ABPI, calf circumference, and ankle circumference, had shown statistically significant differences between the yoga and control groups after 12 weeks of intervention, with moderate to high effect sizes. There were no significant adverse events associated with the intervention. Conclusions: Yoga practices can reduce the symptoms of CVI along with vascular inflammation as indicated by reduced plasma homocysteine. Overall, yoga practices are found to be safe and efficacious for managing CVI. IEC Reference Number: RES/IEC-SVYASA/184/2021 Trial Registration Number (If Clinical Trial): CTRI/2021/02/030944.