OBJECTIVE AND BACKGROUND: The role of psychological disturbance in the pathogenesis of functional dyspepsia is uncertain. We aimed to examine for differences in anxiety, depression and health-related quality of life (HRQOL) between adults with organic (OD) and functional dyspepsia (FD). METHODOLOGY: A prospective, cross-sectional study of Malaysian adults undergoing oesophago-gastro-duodenoscopy (OGDS) for the primary indication of dyspepsia was conducted. Prior to OGDS, locally translated and validated versions of the Hospital Anxiety and Depression Scale (HADS), Nepean Dyspepsia Index (NDI) and Leeds Dyspepsia Questionnaire (LDQ) were administered. RESULTS: 839 patients (mean age 49.6 ± 15.8 years, 55.7% female, ethnic division: Malays 30.5% , Chinese 38.4%, Indians 29.4%) were studied between June 2008 and March 2009. 472 (56.3%) and 367 (43.7%) patients had FD and OD respectively. There was no difference in the mean LDQ score between FD and OD patients (18.6 vs 18.1, P = 0.4). Moderate/severe anxiety was more prevalent in FD compared to OD patients (28.5% vs 23.1%, P = 0.05) but there was no significant difference in depression. Summary scores for the NDI revealed a lower mean value in FD patients compared to OD patients (68.6 ± 19.5 vs 71.4 ± 19.6, P = 0.04). CONCLUSION: Patients with FD have a lower HRQOL compared to those with OD, but this could not be attributed to differences in anxiety nor depression between both groups.