In a prospective single-center cohort from Portugal from 2013–2024 concomitant quadruple therapy (QuadC) and bismuth quadruple therapy (QuadB) achieved H. pylori eradication rates of 93% and 90%, respectively, on intention-to-treat analysis, significantly outperforming standard triple therapy at 74%. Sequential quadruple therapy (QuadS) achieved 84%, with no significant difference versus QuadC or QuadB.