BACKGROUND: The relationship between dyspepsia and psychiatric comorbidity such as anxiety and depression is poorly defined. Previous studies have been limited by lack of standardised diagnostic criteria. AIM: To examine the prevalence and comorbidity of dyspepsia as defined by Rome III (6-month duration) with DSM-IV-TR generalised anxiety disorder (GAD) and major depressive episodes (MDE) in the general population. METHODS: A random population-based telephone survey was done using a questionnaire on symptoms of Rome III Dyspepsia, DSM-IV-TR GAD and MDE and their chronological relationship. RESULTS: Of the 2011 respondents 8.0% currently had Rome III Dyspepsia, 3.8% reported GAD and 12.4% reported MDE respectively. Dyspeptic subjects had a twofold increased risk of GAD (OR = 2.03, 95% CI: 1.06-3.89, P < 0.001) and a threefold increased risk of MDE (OR = 3.56, 95% CI: 2.33-5.43, P < 0.001). MDE and GAD most often coincided with dyspepsia in onset. Dyspepsia (OR = 2.48, 95% CI: 1.65-3.72 P < 0.001), MDE (OR = 2.39, 95% CI: 1.64-3.46, P < 0.001) and female sex (OR = 1.65, 95% CI: 1.21-2.23, P < 0.001) independently predicted frequent medical consultations. GAD independently predicted high investigation expenditure (OR = 4.65, 95% CI: 1.15-18.70, P = 0.03). CONCLUSIONS: With stringently adopted Rome III and DSM-IV-TR criteria, dyspepsia was strongly associated and often coincident in onset with generalised anxiety disorder and major depressive episodes in the community. Excessive healthcare utilisation should alert clinicians to risk of psychiatric comorbidity.