Purpose This study aimed to assess the prevalence, pattern and associated risk factors with dry eye disease (DED) at a tertiary eye care centre in Central India. Methods This prospective cross-sectional study, conducted over 48 months, enrolled patients with systematic random sampling. Evaluation of DED was done with subjective and objective methods comprising of the Ocular Surface Disease Index (OSDI) questionnaire, slit lamp examination, Schirmer's tests and fluorescein tear-film breakup time (FTBUT) test. Patients were categorised into mild, moderate, severe and very severe DED. Association with various etiological factors like age, sex, occupation, diabetes mellitus, autoimmune disorders and any other systemic illness was assessed. The chi-square test/Fischer's exact test was used to analyse categorical data. Bivariate logistic regression analysis was used to calculate the odds ratio (OR). Multivariate analysis was performed to identify independent risk factors. Results A total of 2,560 patients were evaluated, of which 640 patients (25%) had DED. Prevalence was higher in patients aged >50 years, household workers, students, government employees and farmers. Uncorrected refractive status, cigarette smoking, ocular allergy and contact lens usage were associated with increasing odds of developing DED. Conclusion The prevalence of DED was estimated to be 25% in central India. Certain occupations like household workers, students, government employees, farmers, uncorrected refractive status, cigarette smoking, ocular allergy and contact lens use were significant risk factors for dry eyes.