Background: The current cure rates with triple therapy combining a proton-pump inhibitor, amoxicillin and clarithromycin are unacceptably low. Aims: To evaluate the efficacy of a 14-day concomitant therapy as an empirical first-line treatment for curing Helicobacter pylori (Hp) infection in primary care. Methods: Patients from six primary care centers in Catalonia -Spain- were included consecutively. Hp status pre and post treatment was assessed according to local clinical practice protocol. A 14-day concomitant therapy (amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg plus omeprazole 20 mg, all drugs administered twice daily) was prescribed. Adherence to therapy and adverse events were assessed by personal interview. Results: 112 patients were enrolled. Mean age was 46.7 ± 16.1 years. Main indication for treatment was non-investigated dyspepsia (83%). Hp eradication was achieved in 100 of the 112 patients. Eradication rates were 89.3% (95% CI: 81.7–94.1) by intention-to-treat (ITT) analysis and 91.7% (95% CI; 84.6–95.9) per protocol (PP). No major side effects were reported; 104 (92.8%) patients complete the treatment. Forty-seven patients (42%) complained of mild side effects (metallic taste, nausea). Low adherence to treatment (p = 0.004) and significant adverse events (p = 0.004) were the variables associated with treatment failure. Conclusions: In primary care, a 14-day concomitant therapy is highly effective and well tolerated.