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Knowledge about determinants for clinical events in gallstone carriers is missing. The aim of this cohort study was to identify determinants of clinical gallstone events during long-term follow-up of a population unaware of their gallstones.Three randomly selected groups from the general population of Copenhagen (n = 6 037) underwent ultrasound examinations to detect gallstones in the period 1982–1994. Participants unaware of gallstone (n = 595) were followed up for clinical gallstone events through central registers until December 31, 2011. Follow-up length was median 17.5 years and 99.8% complete. Cox regression analyses were performed.Gallstone events occurred in 16.6% participants of whom 7.2% were complicated and 9.4% were uncomplicated. Total events were associated with body mass index. Complicated events were associated with coffee consumption, vocational training, and inversely association to a higher physical activity level when compared with being sedentary. Multiple adjusted models confirmed association for total events and body mass index and for complicated events and physical activity. No significant associations were identified for alcohol, coffee, diet, smoking, or visits to general practitioner and clinical events.Body mass index, vocational training, and physical activity level were associated with clinical events in long-term follow-up of unaware gallstone carriers. Future trials should investigate clinical effects of lifestyle and medical interventions in gallstone carriers.