Objective: To compare the efficacy of triple therapies for H. pylori eradication with verses without Azithromycin in patients with active duodenal ulcer Setting: Department of Medicine, Jinnah Post Graduate and Medical Center, Karachi. Study Design: Randomized controlled Trial Duration of Study: Six months started on Dec. 14, 2013 to June 13, 2014 Subjects and Methods: All patients of either gender with age 30-60 years presented with active duodenal ulcer with H Pylori and duration of symptoms more than 3 mo were enrolled. Group A was prescribed Azithromycin 1 g OD for the first 3 days (total dose 3 g), amoxicillin 1 g bid and omeprazole 20 mg bid (OAA). Group B metronidazole 500 mg bid, amoxicillin 1 g bid and omeprazole 20 mg bid (OAM). Both the therapy was given for 1 wk, followed by monotherapy of Omeprazole 20 mg OD in both groups for 3 wk. At the end of the 8th week endoscopy and urea breath test was performed. Results: Mean age of the patients was 44.06 ± 8.70 years. Mean duration of symptoms of the patients was 5.91 ± 1.36 mo. In patients presented in OAA triple therapy group, efficacy was found in 19 (63.3%) patients whereas, in patients presented in OAM triple therapy group, efficacy was found in 8 (26.7%) patients (p-value 0.004). Conclusion: The efficacy of triple therapies for H. pylori eradication with Azithromycin is more vs. without Azithromycin in patients with active duodenal ulcer.