Aim of the study: Selection of patients for cholecystectomy is hampered by lack of objective criteria. The objectives of this cohort study were to identify if patient, symptoms, or gallstone disease characteristics determined readmission in an unselected cohort with screen-detected gallstone disease and who had experienced a first admission with symptomatic gallstone disease. Methods: Data from three random sampled population-based cohorts were used. At baseline, participants were screened with ultrasound and 664 had gallstones of which 84 had a first admission without cholecystectomy performed. A cohort study was performed with follow-up up for hospital readmissions beyond 30 days through central registers. Age adjusted Cox regression analyses were performed. Results: Readmissions occurred in 60.8% and cholecystectomy was eventually performed in 47.7% of patients. Early readmissions were determined by abdominal pain in the epigastrium (Hazard ratio (HR) 3.63, 95% confidence interval (CI) [1.62;8.12]) and of moderate intensity (HR 2.71, 95% CI [1.20;6.16]). Late readmissions were determined by larger gallstone size, especially when above 10 mm (HR 4.11, 95% CI [1.18;14.3]) and inversely determined by age (HR 0.97, 95% CI [0.95;0.998]). In patients with initially uncomplicated gallstone disease, cholecystectomy was inversely determined by age (HR 0.96, 95% CI [0.93;0.98]). Conclusion: Once gallstones have become symptomatic and caused hospital admission, a persisting high risk for future readmission exists and half of patients end up having cholecystectomy. Pain in the epigastrium, larger gallstones, and younger age determine readmission. These determinants should be tested in future clinical treatment algorithms for gallstone disease.