To examine risk factors for the prevalence of dry eye syndrome in a population-based cohort. The prevalence of dry eye was determined by history at the second examination (1993-1995) of the Beaver Dam Eye Study cohort (N = 3722). The cohort was aged 48 to 91 years (mean +/- SD, 65 +/- 10 years) and 43% male. The overall prevalence of dry eye was 14.4%. Prevalence varied from 8.4% in subjects younger than 60 years to 19. 0% in those older than 80 years (P<.001 for test of trend). Age-adjusted prevalence in men was 11.4% compared with 16.7% in women (P<.001). After controlling for age and sex, the following factors were independently and significantly associated with dry eye in a logistic model: history of arthritis (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.56-2.33), smoking status (past, OR, 1.22; 95% CI, 0.97-1.52; current, OR, 1.82; 95% CI, 1.36-2.46), caffeine use (OR, 0.75; 95% CI, 0.61-0.91), history of thyroid disease (OR, 1.41; 95% CI, 1.09-1.84), history of gout (OR, 1.42; 95% CI, 1.02-1.96), total to high-density lipoprotein cholesterol ratio (OR, for 1 unit, 0.93; 95% CI, 0.88-0.99), diabetes (OR, 1.38; 95% CI, 1.03-1.86), and multivitamin use (past, OR, 1.35; 95% CI, 1. 01-1.81; current, OR, 1.41; 95% CI, 1.09-1.82). Nonsignificant variables included body mass; blood pressure; white blood cell count; hematocrit; history of osteoporosis, stroke, or cardiovascular disease; history of allergies; use of antihistamines, parasympathetics, antidepressants, diuretics, antiemetics, or other drying drugs; alcohol consumption; time spent outdoors; maculopathy; central cataract; and lens surgery. The results suggest several factors, such as smoking, caffeine use, and multivitamin use, could be studied for preventive or therapeutic efficacy. Arch Ophthalmol. 2000;118:1264-1268