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Abstract Background Chronic kidney disease (CKD) is a growing global health problem with faster progression in developing countries such as Iran. Here we aimed to evaluate the prevalence and determinants of CKD stage III+. Methods This research is part of the Khuzestan Comprehensive Health Study (KCHS), a large observational population-based cross-sectional study in which 30,041 participants aged 20 to 65 were enrolled. CKD was determined with estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73m2, based on two equations of Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The multivariate logistic regression was used to evaluate the CKD stage III+ determinants. Results Prevalence of CKD stage III+ is estimated to be 7.1, 5.5, and 5.4% based on MDRD, CKD-EPI, and combination of both equations, respectively. More than 89% of CKD subjects aged higher than 40 years. In regression analysis, age more than 40 years had the strongest association with CKD stage III+ probability (OR: 8.23, 95% CI: 6.91–9.18). Higher wealth score, hypertension, High-Density Lipoprotein levels less than 40 mg/dl, and higher waist to hip ratio were all associated with CKD stage III+ while Arab ethnicity showed a protective effect (OR: 0.69, 95% CI: 0.57–0.78). Conclusion Our findings provide detailed information on the CKD stage III+ and its determinants in the southwest region of Iran. Due to strong association between age and CKD stage III+, within a few decades we might expect a huge rise in the CKD prevalence.