Background: The SARS Cov-2, has emerged as one of the biggest global health threats of the 21st century. It symptomatically varies from having mild to severe symptoms with fever, cough, breathing difficulty, anosmia, diarrhea etc. With the frequent changing protocols and no drug of choice till date, the management of COVID-19 can be structured through some preventive measures/medicines. Aims and Objectives: To assess the efficacy of ASA-20 (Ayush kwath, Samsamani vati, Anu taila) in preventing COVID-19 infection in healthy volunteers as a prophylactic measure among high-risk populations (Health Care Workers/Containment Zone & Quarantined Population) exposed to COVID-19. Materials and Methods: A total of 5000 subjects aged between 18 to 68 years were enrolled in to the study and non randomly divided into two groups. Subjects in Group-A (trial group) were given ASA-20 orally for 30 days along with standard preventive care as recommended by ICMR while subjects enrolled in Group-B (control group) were advised to follow only standard preventive care. Assessment was made based on Immune status questionnaire, general health questionnaire and COVID-19 positivity status during the study period. Follow ups were done on day 1, 15, 30 and 45. Statistical analysis was done by using Chi-square test and Fisher test. Results: 0.80% and 1.79% subjects were found to have tested positive in the trial and control group respectively. The results show that control group is 2.26 times more likely to contract COVID-19 than the trial group. In other words, the medicine is effective in reducing the contraction of COVID-19 by more than half.