Objective: To identify geographic and climatic risk factors associated with exfoliation syndrome (ES). Methods: A retrospective study of 626 901 eye care recipients, dating from 2001 to 2007 from 47 US states in a managed care network. Incident ES cases-patients (NEuro Surveillance (Bulletin Europeen Sur Les Maladies Transmissibles; European Communicable Disease Bulletin)3367) were identified by using billing codes. We assessed the risk of ES by geographic latitude tier in the continental United States and assigned state-level climatic data (eg, ambient temperature, elevation, and sun exposure) according to patients' residential location. The hazard of ES was calculated by using multivariableadjusted Cox proportional hazards regression models. Results: Compared with middle-tier residence, northerntier residence (above 42¡N) was associated with an increased hazard of ES (adjusted hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.94-2.35). Southern-tier (below 37¡N) was associated with a reduced hazard of ES (HR, 0.83; 95% CI, 0.75-0.93). Excluding whites did not change these associations. After adjustment for joint environmental effects, for every 1¡ increase in July high temperature, the hazard of ES decreased by 9% (HR, 0.91; 95% CI, 0.89-0.93); for every 1¡ increase in January low temperature, the hazard decreased 3% (0.97; 0.96-0.98). For each additional sunny day annually, the hazard increased by 1.5% (HR, 1.02; 95% CI, 1.01-1.02) in locations with average levels of other climatic factors. Conclusion: Ambient temperature and sun exposure may be important environmental triggers of ES. ©2011 American Medical Association. All rights reserved.