Aims: Taiwan has the highest incidence and prevalence of end-stage renal disease worldwide. Haptoglobin (Hp) has a role in renal protection, and there are known differences in the function of different Hp alleles. We aim to study the association between Hp genotype and chronic kidney disease (CKD) in Taiwan. Methods: We performed one hospital-based, age-matched case-control study of 213 patients with CKD and 213 controls to evaluate the association between Hp polymorphism and CKD. Three major Hp genotypes were determined using polymerase chain reaction and electrophoresis. An unconditional logistic regression model was used to identify the associated risk factors for the development of CKD. Results: The frequency of Hp2-2 genotype and Hp2 allele was significantly higher in the CKD group than in controls (p = 0.032 and 0.024, respectively). After adjustment for covariates, the Hp2-2 genotype (vs. Hp1-1; OR 3.841) remained significantly associated with the development of CKD, together with diabetes (OR 3.131), hypertension (OR 1.748) and dyslipidemia (OR 1.646). Conclusion: This present study shows that Hp2-2 genotype is an independent risk factor for CKD. Determination of the Hp genotype may be of potential value to the prediction of genetic risk for CKD.