Infection with H. pylori has been linked with chronic active gastritis, peptic ulcer disease, adenocarcinoma and Non-Hodgkin's lymphoma of the stomach. Eradication of this organism has been recommended for patients with peptic ulcer disease, low-grade gastric mucosa-associated lymphoid tissue lymphoma, atrophic gastritis, unexplained iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, as well as first-degree relatives of gastric cancer patients. Guidelines still recommend using triple therapy regimen of PPI, clarithromycin and amoxicillin/metronidazole twice daily for 7 to 14 days. Over the years, it has become clear that the first-line triple therapy is losing efficacy worldwide with per protocol (PP) and intent-to-treat (ITT) eradication rates of less than 80%. In light of the low eradication rates of this regimen, quadruple regimens (bismuth and non bismuth based) or alternative fluoroquinolones-based regimens evolved in an attempt to increase the eradication of H. pylori. Most of the new quadruple regimens are clarithromycin-based. Quadruple therapies improved eradication rates to 85-90% but the increasing resistance of H. pylori to clarithromycin rendered the above-mentioned regimens suboptimal. Many attempts to increase the number of antibiotics in treatment regimens were faced with intolerability by patients of the large number of pills and increasing side effects (metallic taste, nausea, etc.). Considering the above, a capsule containing 3 agents (Pylera®) containing 125mg metronidazole, 140mg bismuth subcitrate potassium, and 125mg tetracycline was made available. The importance of such capsule lies in the 3 in 1 packaging and in the avoidance of clarithromycin use and hence the low risk of resistance. The efficacy of the Pylera capsule was studied in a randomized control trial, in which a quadruple Pylera therapy (Pylera capsule and a PPI) was evaluated against the standard triple regimen. In the study, 3 three-in-one capsules were taken four times daily (after meals and at bedtime). An omeprazole capsule was taken with the three single three-in-one capsules after morning and evening meals. Quadruple therapy (Pylera-based) provided superior eradication rates when compared to the standard triple therapy (as high as 80% eradication rate versus 55% on ITT) with similar safety and tolerability [1]. In the aforementioned study, patients on quadruple therapy were taking the sum of 14 pills per day. This big number of pills per day is too high and may threaten compliance and adherence in real life situations outside of controlled clinical trials. This is evidenced by the difference in the PP and ITT eradication rates (93% and 80% respectively) that can be attributed to the load of pill load.