OBJECTIVES: To evaluate the impact of dry eye disease (DED) on health-related quality of life, work productivity, daily activities, and healthcare resource use. METHODS: Data were analyzed from participants (≥18 years) of the 2013 National Health and Wellness Survey. Participants were classified as: Diagnosed-DED, Symptomatic-Undiagnosed (undiagnosed but experienced DED symptoms), and Non-DED (no DED diagnosis/symptoms). Outcome measures included: the Short Form (SF)-36 health survey (mental component summary [MCS], physical component summary [PCS]; 0-100 scale, higher=better health status), Work Productivity and Activity Impairment (WPAI) questionnaire (absenteeism, presenteeism, impairment in daily activities in past 7 days), and healthcare resource use. Multivariate regression was used to estimate adjusted group effects relative to the Non-DED group for each outcome, controlling for age, sex, insurance type, socio-demographic and lifestyle factors, and comorbidities. RESULTS: There were a total of 74,095 participants (mean age 48 years (SD 17), 52% women): 5,042 Diagnosed-DED, 1,785 Symptomatic-Undiagnosed, and 67,268 Non-DED. For each measure, Diagnosed-DED and Symptomatic-Undiagnosed participants had significantly worse outcomes than the Non-DED group (P<0.001 for all comparisons). For the Diagnosed-DED, Symptomatic-Undiagnosed, and Non-DED groups, mean (SD) scores for the SF-36 were: PCS (45.3 [10.6], 48.8 [9.5], 50.7 [9.4]); MCS (48.1 [11.4], 44.6 [11.6], 49.1 [10.5]). Mean (SD) overall work loss (assessed for N=37,951 employed participants) was: 23.4% (28.3), 20.3% (26.8), and 15.0% (25.0), respectively. In multivariate analysis, between-group differences were significant for the presenteeism subscale (P<0.0001) but not for absenteeism (P=0.6419). For activity impairment, mean (SD) scores were: 34.1% (31.1), 28.2% (29.3), and 21.3% (27.8), respectively. Mean (SD) annual medical provider visits were: 12.5 (13.9), 8.5 (13.2), and 6.9 (10.5).  CONCLUSIONS: DED impacted patients by lowering their overall health-related quality of life, increasing work loss, impairing daily activities, and requiring more medical visits. Effects on work loss were predominantly due to reduced productivity while at work.