Currently, peptic ulcers are widely studied as an infectious disease caused by Helicobacter pylori primarily due to 3 supporting evidences, and this etiology may explain the other 3 observations, but cannot confront the challenges of the 15 major characteristics and the other 75 observations/phenomena of peptic ulcers. To address the challenges, a recently published Complex Causal Relationship with its accompanying methodologies was applied to analyze existing data. Peptic ulcers are identified as a psychosomatic disease triggered by psychological stress, where Helicobacter pylori plays a secondary role in only the late phase of ulceration. This new etiology elucidated all the 15 major characteristics and 81 observations/phenomena of peptic ulcers in a series of 6 articles. This sixth article focuses exclusively on the controversies surrounding the role of Helicobacter pylori in peptic ulcers. In-depth analyses find that all the 3 evidences supporting “peptic ulcers are an infectious disease caused by Helicobacter pylori” are deceiving, and 2 of the 3 explainable observations may have been misinterpreted. Meanwhile, the definitions of ‘etiological factor’ and ‘causality’ do not support ‘H. pylori infection is an etiological factor of peptic ulcers’, and existing literatures have presented a controversial view on the role of Helicobacter pylori in peptic ulcers. Interestingly, if “peptic ulcers are an infectious disease caused by Helicobacter pylori” is considered an illusion, all the characteristics of the disease, along with all the clinical, epidemiological, and laboratory observations/phenomena, can be fully understood. This illusion has misguided peptic ulcer research over the past 36 years with little progress in the field, and that may represent a widespread situation in modern medical research, resulting in a direct interference with the true understanding of disease. Evidently, keeping the concept “illusion” in mind may help remove a huge obstacle that impedes medical advance, thereby facilitating the in-depth study of disease.