OBJECTIVES: To examine factors associated with dry eye disease (DED) in the US. METHODS: We conducted a cross-sectional survey of 4000 participants in the Women’s Health Study and Physicians’ Health Studies with diagnosed DED or severe symptoms. We assessed the current level of symptoms by the Ocular Surface Disease Index (OSDI) and Symptom Assessment in Dry Eye (SANDE) questionnaires, diagnosis, co-morbidities, treatments, and patient satisfaction. RESULTS: 3390 (84.8%) subjects returned questionnaires. 2099 participants reported a diagnosis of DED, and 1291 denied DED diagnosis (73.9% of these had reported DED diagnosis previously). Among 451 subjects selected based on severe symptoms alone, 114 (25.3%) reported a new diagnosis of DED, which was more strongly associated with severe symptoms by SANDE>40 (OR=2.24, p=0.001), than by OSDI 33-100 (OR=1.38, p=0.25). Blepharitis (OR=2.03, p=0.05) was also associated with new DED diagnoses. Among those who currently denied DED diagnosis, 15.9% had severe (SANDE>40) and 40.4% had mild-moderate symptoms (SANDE 15-40). Adjusting for age and sex, participants with symptoms only were less likely than diagnosed patients to have an eye exam ≥1x/year (OR=0.71, p=0.002), use antidepressants (OR=0.76, p=0.04), artificial tears (OR=0.67, p=0.0002), or other DED treatments (OR=0.65, p=0.0001); and more likely to report refractive surgery (OR=1.67, p=0.02), and contact lens wear (OR=2.51, p<0.0001). In age- and sex-adjusted models including all respondents, those who currently reported DED diagnoses were more likely to have an eye exam ≥1x/year (OR=1.42, p=0.0003), severe symptoms (SANDE >40, OR=2.00, p<0.0001), blepharitis (OR=1.41, p=0.007), use antidepressants (OR=1.43, p=0.003), artificial tears (OR=2.01, p<0.0001), or other DED treatments (OR=1.70, p<0.0001); and less likely to use glaucoma medications (OR=0.82, p=0.02). CONCLUSIONS: These observations suggest the possibility of under-diagnosis of DED, and are also consistent with a milder and/or more intermittent type of DED. Individuals with diagnosed DED are more likely to have severe symptoms, despite therapy.