Acne vulgaris is one of the most common skin disorders. It mainly affects adolescent, though may present at any age. The conventionally used dose of isotretinoin in acne causes significant dose-related adverse effects. Low-dose isotretinoin has been used successfully, in mild to moderate papulopustular acne. To observe whether the addition of an antibacterial enables use of isotretinoin in low doses even in moderate to severe acne. An open-label, non-comparative study was carried out for 24 weeks. Eighty two teenagers with moderate to severe papulo-pustular acne vulgaris were enrolled. These patients were treated with a combination of low-dose isotretinoin (0.3mg/kg/day) and pulsed oral azithromycin (500mg/day over three consecutive days in each week for one month. No topical treatment was permitted. Response to treatment was assessed at monthly intervals and was recorded as a percentage decrease in overall severity of disease. Treatment was continued to complete clearance of lesions or to 24 weeks. All patients were also evaluated at six months post-treatment. Eighty (97.56%) patients had complete clearance of disease activity after treatment duration of 24 weeks. Only two (2.43%) patients had a relapse of disease during the post-treatment follow-up period. Four (4.87%) patients were observed with adverse effects. Three (3.65%) patients had initial aggravation of disease that was managed with oral betamethasone and this disappeared with continuation of treatment. A combination of low-dose isotretinoin and oral azithromycin pulse is effective in moderate to severe acne.