Introduction: Non-cardiac chest pain (NCCP) is mainly related to oesophageal disease, and in spite of being a common condition in Mexico, information regarding it is scarce. Aim: To assess the clinical characteristics and health-related quality of life of patients with NCCP of presumed oesophageal origin. Material and methods: Patients with NCCP of presumed oesophageal origin with no previous treatment were included in the study. Associated symptoms were assessed and upper gastrointestinal endoscopy and 24-hour oesophageal pH monitoring were performed to diagnose gastroesophageal reflux disease, while oesophageal manometry was used to determine oesophageal motility disorders. The SF-36 Health-Related Quality of Life (HR-QoL) questionnaire was completed and its results compared to a control group without oesophageal symptoms. Results: The study included 33 patients, of which 61% were women, and the mean age was 46.1 (± 11.6) years. Causes of NCCP were gastroesophageal reflux disease in 48%, achalasia in 34%, and functional chest pain in 18%. The average progression time for chest pain was 24 (2-240) months, with ≤3 events/week in 52% of the patients. The most frequent accompanying symptoms were: regurgitation (81%), dysphagia (72%) and heartburn (66%). Patients with NCCP show deterioration in HR-QoL compared to the control group (P = .01), regardless of chest pain aetiology. The most affected areas were general perception of health, emotional issues, and mental health sub-scale (P > 0.05). Conclusions: In our population, patients with NCCP show deterioration in HR-QoL regardless of the aetiology, frequency, and accompanying symptoms.