Context: Chronic kidney disease (CKD) patients are at high risk of drug-drug interactions (DDIs) that may require dose adjustments or the avoidance of drug combinations. Aim: To evaluate DDIs among chronic kidney disease patients of nephrology unit in the University of Nigeria Teaching Hospital (UNTH), Enugu in South-East Nigeria. Settings and Design: This study was a retrospective review of CKD patients who received treatment at the nephrology unit of UNTH between January 2004 and December 2014. Methods and Materials: The drug-drug interactions (DDIs) of the prescribed drugs were classified using the Medscape drug interaction checker. Statistical Analysis used the data were analyzed using the Statistical Package for Social Sciences (SPSS) for Windows version 16.0 (SPSS Inc, Version 16.0, Chicago, USA). The predictors of the DDIs were explored through linear regression with number of DDIs as the dependent variable. Results: A total of 898 DDIs were identified from the folders of the 169 CKD patients that were eligible. Majority were above 50 years old and in renal disease stage 4 or 5. Furosemide, lisinopril and amlodipine were the most frequently prescribed drugs and had the greatest likelihood for nephrotoxicity. The number of medications and hypertension (as co-morbidity) were the independent predictors of DDIs among the patients. Majority of the DDIs (64.14%) were significant. The most common interactions were between lisinopril and furosemide; furosemide and calcium carbonate; lisinopril and calcium carbonate. Conclusion: The prevalence of significant DDIs was high among the renal patients. The major determinants of the DDIs were the number of medications and the presence of hypertension as co-morbidity.