Background: Irritable bowel syndrome is a common problem known to have a complex relationship with psychological disorders and other physical symptoms. Little information, however, is available concerning physical and psychological comorbidity in irritable bowel syndrome patients studied over an extended period. Aim: To evaluate physical and psychological morbidity 2 years before and during 6 years after the time of diagnosis in incident cases of irritable bowel syndrome and control subjects. Methods: A matched cohort study was implemented in 123 general practices using the General Practice Research Database. Irritable bowel syndrome cases (n = 1827) and controls (n = 3654) were compared for 2 years before and 6 years after diagnosis. Results: The age-standardized incidence of irritable bowel syndrome in patients over 15 years of age was 1.9 per 1000 in men and 5.8 per 1000 in women. From 2 years before the date of diagnosis, more irritable bowel syndrome cases (13%) than controls (5%) consulted with depression or were prescribed antidepressant drugs. Consultation and prescription rates for anxiety were also higher before diagnosis, and both anxiety and depression remained prevalent up to 6 years after diagnosis. Asthma, symptoms of urinary tract infection, gall-bladder surgery, hysterectomy and diverticular disease were recorded more frequently in irritable bowel syndrome patients, who were also more likely than controls to be referred to hospital. Conclusions: People who are diagnosed with irritable bowel syndrome experience more anxiety and depression and a range of physical problems, compared with controls; they are more likely to be referred to hospital.