The aim of this study was to assess risk factors for primary Helicobacter pylori antibiotic resistance by an extended anamnesis. In total, 519 H. pylori strains from untreated symptomatic adults who answered a questionnaire were evaluated. Strain susceptibility was assessed by a breakpoint susceptibility test. Primary resistance rates were 29.5 % for metronidazole, 17.9 % for clarithromycin, 7.3 % for metronidazole+clarithromycin, 4.0 % for tetracycline and 10.8 % for ciprofloxacin. On multivariate analysis, younger (≤65 years) age was an independent predictor for metronidazole resistance. To our knowledge, for the first time, being a member of the health-care profession was revealed as a risk factor for H. pylori resistance to metronidazole and both metronidazole and clarithromycin. Respiratory and urinary tract infections were independent predictors of clarithromycin and ciprofloxacin resistance, respectively. The presence of co-infections was an independent risk factor for clarithromycin, metronidazole and ciprofloxacin resistance. Surprisingly, female sex was the only predictor for tetracycline resistance. The antibiotic resistance rates were not associated with disease type, place of residence, birthplace, educational level, non-steroidal anti-inflammatory drug or proton pump inhibitor use, smoking or dietary factors, such as consumption of coffee, yogurt, green tea, raw garlic, raw onion, honey or meat. There was a trend for higher metronidazole resistance in strains from diabetic patients. In conclusion, the extended anamnesis of H. pylori-positive patients should include data on patient age, sex, whether they are in the health-care profession, co-infections and possibly diabetes to improve the choice of empiric therapy. Tailored treatment based on the extended anamnesis is suggested, and susceptibility testing of the strains is recommended for patients at risk for antibiotic resistance, especially to clarithromycin, fluoroquinolones or both metronidazole and clarithromycin.