Javier P. Gisbert, Pablo Parra, Olga P. Nyssen
BACKGROUND: Classic bismuth quadruple therapy (BQT)-the combination of a proton pump inhibitor, bismuth, tetracycline, and metronidazole-is a standard regimen for treating Helicobacter pylori infection. AIMS: This review addresses practical questions regarding its current role in managing the infection. METHODS: A comprehensive bibliographic search was conducted to identify studies evaluating the efficacy, safety and optimization of BQT in different clinical contexts. RESULTS: BQT is a cornerstone of H. pylori eradication, combining agents with complementary mechanisms of action and maintaining high efficacy even in the presence of antibiotic resistance. Optimal acid suppression with a double proton pump inhibitor dose twice daily maximises therapeutic success. When tetracycline is unavailable, minocycline may serve as an alternative, whereas doxycycline is not recommended due to lower efficacy. Ten-day regimens achieve eradication rates comparable to 14-day courses, with similar or better tolerability. The three-in-one single-capsule formulation simplifies administration, enhances adherence, and maintains high efficacy (> 90%). BQT is endorsed as first-line therapy in most international guidelines, particularly in regions with clarithromycin resistance exceeding 15%, and remains the most reliable rescue option after failure of clarithromycin- or fluoroquinolone-based regimens. It is also the treatment of choice for patients with penicillin allergy. The regimen is generally well tolerated, with mostly mild, transient and gastrointestinal adverse events. CONCLUSIONS: BQT remains the most effective, safe, and practical regimen for H. pylori eradication, ensuring high cure rates across diverse resistance patterns and clinical settings. Simplified formulations further improve convenience and adherence, reinforcing its role as a globally applicable therapy.