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To obtain long-term cumulative incidence estimates of time to conversion of clinically unilateral to bilateral exfoliation syndrome (ES).A retrospective, longitudinal cohort study of 35 patients with clinically unilateral ES from the private office of one author. Diagnosis of ES was made between 1968 and 1998. On return visits a careful search for ES in the nonexfoliative fellow eye was made by the same author in a semidark room using a slit lamp and maximal pupillary dilatation. Cumulative incidence of converting to bilateral ES was calculated, taking death into account as a competing risk.Cumulative incidence of conversion to bilateral ES was 0.11 (95% CI, 0.03–0.25) at 5 years, 0.36 (95% CI, 0.15–0.57) at 10 years, and 0.52 (95% CI, 0.27–0.93) at 15 years when the day of examination was taken to be the day of conversion, and 0.14 (95% CI, 0.04–0.29) at 5 years and 0.52 (95% CI, 0.26–0.73) at 10 years when analysis was based on conversion taking place at the midpoint between the last two visits. The median age at conversion was 72 years (range, 66–86), and the median age of patients remaining clinically unilateral was 77 years (range, 57–90). Factors associated with time to conversion depended on the strategy of the analysis and included higher age at first visit and larger IOP difference between the involved and uninvolved eye.A large proportion of patients with clinically unilateral ES will not convert to bilateral involvement in long-term follow-up. Immunohistochemical studies suggest that local factors must either expedite ES or slow it down in one eye to explain the frequently longstanding asymmetric involvement, and a difference in initial aqueous outflow facility might be examined as one candidate.