Presently, there is no published information on the antimicrobial susceptibility pattern of H. pylori strains in Ethiopia to guide the choice of drug for therapy. Therefore, it is becoming clinically relevant to test the in vitro susceptibility of H. pylori clinical isolates prior to treating patients. Susceptibility testing was performed on 50 clinical H. pylori isolates obtained from adult dyspeptic patients referred to the gastrointestinal (GI) Clinic of Tikur Anbassa University Hospital. Five antibiotics were evaluated, by using the Episolmeter test (E-test). The antibiogram of 50 H. pylori clinical isolates showed that all strains were sensitive to clarithromycin, erythromycin and tetracycline, while 38/50 (76%) and 3/50 (6%) of the strains were resistant to metronidazole and amoxicillin, respectively. Infection by metronidazole or amoxicillin resistant H. pylori is an important factor leading to treatment failure. Testing of all H. pylori clinical isolates to metronidazole and amoxicillin is recommended. If it is not possible to perform susceptibility tests on each clinical isolate, a program to survey the prevalence of resistance should be implemented in a given area or population. When treatment of H. pylori infection is indicated in dyspeptic patients, the potential availability, simplicity of use, safety and low cost of the antimicrobial agents have to be taken into account.