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 2 h [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.