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Background: Taiwan has the highest incidence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. Chinese herbal medicine (CHM) has been linked to CKD/ESRD in Taiwan. The specific effects and frequency of CHM on the risk of CKD are unknown. Methods: A hospital-based case‐control study was performed from August 2006 through December 2009. The cases were consecutive nephrology outpatients 20years of age or older, with a first-time diagnosis of CKD, and without cancer or pre-existing renal disease. The controls were randomly selected outpatients that did not have CKD and were matched 1:1 to cases for age, gender and date of outpatient visit. Results: Four hundred and twenty-four patients were recruited. Among 212 cases, 23.6% took non-prescribed CHM, compared to 6.6% among the controls (p<0.001). Multivariate analysis showed that illiteracy [odds ratio (OR) 6.3, 95% confidence interval (CI) 2.4–16.6], hypertension (OR 5.4, 95% CI 2.9–9.8) and occasional use of non-prescribed CHM (OR 6.2, 95% CI 1.8–21.6) were positively associated with CKD, whereas regular exercise was inversely associated with CKD (OR 0.5, 95% CI 0.3–0.9). Conclusion: Occasional use of non-prescribed CHM was associated with the risk of CKD in Taiwan. [Copyright &y& Elsevier]