Background and aims To quantify the relative contribution of environmental, clinical, infection and psychosocial factors in the persistence of gastrointestinal (GI) symptoms among new patients presenting to primary care. Methods We conducted a population-based prospective cohort study of 4986 adults aged 25-65 years. The study team obtained permission from the participants to monitor their general practice records for consultation with GI symptoms and to contact them at that time. Group 1 (n=177) patients completed a postal questionnaire, whereas those in group 2 (n=191) completed an identical questionnaire and provided a blood and stool sample. The participants were followed up for 1 and 6 months postconsultation. Results Of 610 (12.2%) participants who consulted, 368 (60.3%) agreed to participate. Two hundred and eighty participants (76.1%) completed 1 and 6-month follow-up questionnaires and 106 (37.9%) had persistent (present 1 and 6 months postconsultation) GI symptoms. After adjusting for age, sex, area of residence and duration of symptoms before consultation, symptom persistence was independently predicted by high levels of psychological distress [odds ratio (OR): 2.5, 95% confidence interval (CI): (1.1-5.3)], symptom episode duration of more than 2h [OR: 3.1, 95% CI: (1.3-7.1)] and symptom interference with daily activities [OR: 2.3, 95% CI: (1.1-4.8)]. Changing diet [OR: 0.2, 95% CI: (0.1-0.9)] and recent gastroenteritis or food poisoning [OR: 0.2, 95% CI: (0.1-0.98)] were associated with protective effects. Infection was not associated. Exposure to three or more of these factors identified 87.3% (n=92) of the participants with persistent symptoms. Conclusion The factors measured at the time of consultation with GI symptoms can accurately predict those patients at increased risk of persistent symptoms up to 6 months later. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.