The increasing antimicrobial resistance of Helicobacter pylori jeopardizes the efficiency of the classical eradication triple therapy. In this article we assessed the primary resistance rates of Helicobacter pylori to the commonly used antibiotics for eradication in the area of Brussels and determined prospectively, through a questionnaire, the possible risk factors for resistance. Gastric biopsies were taken for histology and culture in all adult patients in whom Helicobacter pylori was searched from February 2009 to April 2010 at the UZBrussel hospital. Clinical and demographic data were collected through a questionnaire. Histology was positive in 222 out of 507 patients tested (43.7%). Culture was successful in 189 patients with a positive histology (85.1%), 4 patients had a positive culture with a negative histology. Resistance to clarithromycin, metronidazole, ciprofloxacin, and amoxicillin was tested. Primary resistance rates were 13.3% for clarithromycin, 26.1% for metronidazole, 23.9% for ciprofloxacin, 0.8% for amoxicillin. Dual resistance to claritromycin and metronidazole was seen in 3.9%, triple resistance (claritromycin, metronidazole and ciprofloxacin) in 1.7% and resistance to the 4 antibiotics in 0.6% of patients. We conclude that there is a decreasing resistance for clarithromycin, metronidazole resistance is stable and rapidly increasing ciprofloxacin resistance. Resistance to any of the tested antibiotics was not associated with origin, age, gender, number of siblings, level of education or status (p > 0.05).