BACKGROUND: Diabetic nephropathy is defined as patients with diabetes mellitus who have persistent proteinuria for at least three consecutive measurements per year, a high blood creatinine level (>130 mol/l), or a decrease in glomerular filtration rate (<60 ml/min). Limited studies were done in Ethiopia on determinants of diabetic nephropathy among diabetic patients. Therefore, this study aimed to identify determinants of nephropathy among adult diabetic patients on follow-up at public hospitals in Addis Ababa, Ethiopia, 2022. METHODS: A hospital-based unmatched case-control study design was conducted from 6 September to 9 November 2022, among diabetic patients on follow-up at public health hospitals in Addis Ababa. Using consecutive sampling techniques, a total of 442 (353 controls and 89 cases) were recruited, with a control-to-case ratio of 4:1. The data were collected using a structured and interview-administered questionnaire and variables like high-density lipoprotein, low-density lipoprotein, Glycated hemoglobin, and type of diabetes were extracted from the medical records of the patients using a checklist. The collected data were entered into Epidata 3.1 and analyzed by STATA version 15.0. Variables with a -value < 0.25 in the bivariable logistic regression were selected for the final model. In multivariable logistic regression model fitting, variables with a -value < 0.05 with 95% CI adjusted odds ratio have declared statistically significant risk factors of diabetic nephropathy. RESULTS: In this study, out of 442 study participants, 334 controls and 89 cases were included in the analysis, with a response rate of 94.6% and 100%, respectively. The majority of the study participants were 92.13% of cases and 84.13% of controls; 7.87% of cases, and 15.87% of controls were type 2 diabetes mellitus. Age 65 and above years old (AOR: 2.42; 95% CI: 1.28, 4.57); Smoking cigarette (AOR: 2.22; 95% CI: 1.18, 4.16); Non-adherent to diet (AOR: 2.11; 95% CI: 1.15, 3.84); Drinking alcohols (AOR: 1.95; 95% CI: 1.07, 3.52); Duration with diabetes more than 10 years (AOR: 3.39; 95% CI: 1.76, 6.54); Poor glycemic control (AOR: 2.19; 95% CI: 1.23, 4.28); and Low-density lipoprotein (AOR: 2.97; 95% CI: 1.69, 5.28) were found to be statistically significant risk factors of nephropathy among diabetic patients. CONCLUSION: This study found that old age, smoking cigarettes, non-adherence to diet, duration of diabetes, alcohol drinking, Glycated hemoglobin A1C, and high low-density lipoprotein were risk factors for nephropathy. Hence, continuous health education on lifestyle modifications and diabetic-related complications in each follow-up visit via front-line health professionals are very essential to avert the problem.