PURPOSE: To estimate the prevalence and determine risk factors for dry eye disease (DED) in geographically diverse regions of India. METHOD: A population based cross-sectional study was conducted on people aged ≥40 years in plain, hilly and coastal areas. Dry eye assessment by objective [tear film break-up time (TBUT), Schirmer I, corneal staining] and subjective [Ocular Surface Disease Index (OSDI)] parameters was performed with questionnaire-based assessment of exposure to sunlight, cigarette smoke, indoor smoke. The prevalence of DED with age, sex, occupation, location, smoking, exposure to sunlight, indoor smoke, diabetes, hypertension, was subjected to logistic regression analysis. RESULTS: 9,735 people (age 54.5 ± 0.1 years; range 40-99, males 45.5%) were included. The prevalence of DED was 26.2%, was higher in plains (41.3%) compared to hilly (24.0%) and coastal area (9.9%) (p < 0.001) and increased with age (p < 0.001), female gender (p < 0.001), smoking (p < 0.001), indoor smoke (p < 0.001), diabetes (p-0.02), hypertension (0.001), occupations with predominant outdoor activity (p-0.013) and increasing exposure to sunlight (trend). Multi-logistic regression showed a positive association with female sex (OR-1.2, CI-1.01, 1.4), exposure to indoor smoke (OR-1.3, CI-1.1, 1.5), smoking (OR-1.2; CI-1.03, 1.3), prolonged exposure to sunlight (OR-1.8, CI-1.5, 2.2), hypertension (OR 1.3, CI-1.2, 1.4), diabetes (OR-1.2, CI-1, 1.5) and negative association with region - hilly (OR-0.5, CI-0.4, 0.6) and coastal (OR-0.2; CI-0.1, 0.2), and BMI (OR-0.8, CI-0.7, 0.9). CONCLUSION: DED is common in population ≥40 years of age. Its prevalence is affected by extrinsic (geographic location, exposure to sunlight, smoking, indoor smoke) and intrinsic (age, sex, hypertension, diabetes, BMI) factors.