Introduction: Acne vulgaris is a chronic inflammatory dermatosis caused by Propionibacterium acnes. Clinicians are constantly attempting to discover the best antibiotic regimes in treating acne vulgaris. This study compares two regimens in terms of efficacy, tolerability, compliance and recurrence rate to make recommendation on which is the best regime. Methods: An open-labelled prospective randomized investigator-blinded interventional study was carried on moderate acne vulgaris patients. Patients were assigned to treatment arm at enrolment followed by follow-up and maintenance visits. Demographic data were collected at enrolment and questionnaire enquiring acne condition, general health and quality of life impairment were filled at every visit followed by blinded dermatologist assessment. Antibiotic tablets were provided based on assigned arm until follow-up 3. Results: 26 mild acne vulgaris patients aged 17 to 29 years were recruited. Physician assessment based on GAGS and photo assessment analysis showed an overall significant change (p<0.05) with decreasing trend indicating that the treatment is statistically effective. However, no significant differences (p>0.05) were found between regimens. Similarly, patient self-perceived assessment and CADI assessment also showed overall significant changes (p<0.05) with increasing trend indicating improvement in acne condition but no significant differences (p<0.05) between regimens. Conclusion: Neither regimen were significantly more efficacious than another. In view of cost, oral azithromycin 500mg daily for consecutive 4 days monthly is suggested as a better option.