Aim: To assess the efficacy and safety profile or oral azithromycin with oral doxycycline in patients with refractory meibomian gland dysfunction. Material and method: This prospective randomized control study comprised of 60 patients attending the outpatient Department of Ophthalmology at Subharti Medical College. All cases underwent a detailed evaluation including visual acquity, anterior segment slit lamp examination of lid margins, tear minuscus, conjunctiva, cornea and tear film. Patients aged 18-70 were included in the study and the age matched randomization was done in two groups i.e. Group A (Oral Azithromycin 500mg on day 1 and then 250mg per day for next 4 days) and Group B (Doxycycline 100mg twice a day for 7 days and then 100mg once a day for next 21 days). All patients underwent complete ophthalmic examination and the signs and symptom scores were recorded prior to the treatment subsequently at 1 month, 3 months and 6 months post treatment. Results: At last follow-up, there was distinct improvement in all the symptoms and mean score of all the signs in both the groups. The decrease in mean score was more in group A as compared to group B, however statistically significant was found in bulbar conjunctival redness, meibomian gland plugging, eyelid margin redness and ocular surface staining. Side effects were more in Doxycycline group as compared to Azithromycin group.