Background: The menace of COVID-19 has put a huge burden on health care system predisposing health care workers engaged in management to COVID-19 infections. The nonavailability of effective drug against COVID-19 warrants extra cover as prophylactic therapy for health care workers, especially against transmission from asymptomatic patients. Hydroxychloroquine (HCQ) for prophylaxis of COVID-19 had been advocated by some researchers. Hence, in this project, evaluation of HCQ as preventive strategy for healthcare workers against COVID-19 infection was studied. Materials and Methods: HCQ was prescribed as a prophylactic therapy as per the advisory of National Task Force of Indian Council of Medical Research, India. The data regarding consumption profile, COVID-19 infection and adverse drug reaction profile of HCQ in healthcare workers was collected. Results: Record of 4,239 health workers with hydroxychloroquine consumed was available till date. 139 subjects were dropped out of study as they did not consume the HCQ tablets. 93 heath workers (2.19%) were infected with COVID-19 infection but in early weeks of prophylactic therapy and were asymptomatic. A few of them (08 patients) had mild symptomatic manifestation with RT- PCR reported positive for SARS-CoV-2. No mortality was reported as among healthcare workers, engaged in management of COVID-19 patients at the tertiary care institute in Jaipur, India. HCQ prophylaxis in standard doses produced predominantly gastrointestinal side effects in 20 subject and headache in 10 health workers. Conclusion: The present study showed that HCQ prophylaxis is safe and effective in standard doses against COVID-19 infection. The frontline workers engaged in management of COVID-19 may be given HCQ prophylaxis as an extra cover. However, it’s broadening usage as preventive strategy, in general for people especially in cardiovascular incidences; require enhanced research and further validation.