Objective: To evaluate the characteristics of central corneal thickness (CCT) and its association with age, gender, and intraocular pressure in rural and urban South Indian populations. Design: Population-based cross-sectional study. Participants: Seven thousand seven hundred seventy-four subjects (rural-to-urban ratio, 3924:3850) aged 40 years and older were examined at a dedicated facility in the base hospital. Intervention: All subjects underwent a complete ophthalmic examination that included CCT measurements with an ultrasonic pachymeter and applanation tonometry. Main Outcome Measures: Central corneal thickness. Results: Of the 7774 subjects examined, 974 had undergone cataract surgery and were excluded. The remaining 6800 were bilaterally phakic, of which 46 were excluded (17 glaucoma subjects receiving treatment, 12 with corneal pathologic features and 17 with incomplete data) and 6754 subjects data were analyzed. The mean CCT for the population was 511.4±33.5 μm, and CCT in males (515.6±33.8 μm) was significantly (P = 0.0001) greater than females (508.0±32.8 μm). The CCT was significantly greater (by 18 μm) in the urban population and decreased with age in both genders (P<0.0001). The decrease per decade was 4.34 μm (95% confidence interval [CI], 3.24-5.44) in the rural population and 2.41 μm (95% CI, 1.25-3.53) in the urban population. A 100-μm increase in CCT was associated with a 1.96-mmHg increase in intraocular pressure in the rural population, versus 2.45 mmHg for every 100 μm in the urban population. Conclusions: In this population-based study, females and subjects living in a rural area had thinner corneas. A negative association with age and a positive association with intraocular pressure were seen. These findings will have implications in the diagnosis and management of glaucoma in this population. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.