Background: Chronic complications of diabetes mellitus, such as cardiovascular diseases, neuropathy, retinopathy, and nephropathy, have a profound impact on the overall well-being and quality of life of patients. Identifying determinant factors associated with the chronic complication of diabetes mellitus is critical for prevention. This study aimed to identify the determinant factors for chronic complications of Diabetes Mellitus among diabetic patients at Dessie Comprehensive and Specialized Hospital, Northeast Ethiopia. Methods: An institution-based case control study was conducted from February to June 2021 at Dessie Comprehensive and Specialized Hospital. We included 357 participants with 68 cases and 272 controls (1:4 ratio), selected using consecutive sampling technique. Cases were diabetic patients with chronic complications, while controls were diabetic patients without such complications. Data were collected through interviewer administered questionnaire and review of patient medical records. Binary logistic regression model was used to examine the associated factors. The association was measured using odds ratio with a 95% confidence interval (CI), and statistical significance was declared at a p-value < 0.05. Result: From the total participants, 191(56.2%) were males and 149 (43.8%), were females. We found that chronic complications of diabetes mellitus were positively associated with being unmarried (adjusted odds ratio (AOR)=4.5[2.1-9.5]), alcohol drinking (AOR=3.8[1.9-7.6]), physical inactivity (AOR=3.1[1.5 6.4]), more than 10 years duration of diabetes mellitus (AOR=3.1[1.3-7.2]), and body mass index BMI ? 25kg/m2 (AOR=2.3[1.2-4.3]). Conclusion: This study identified significant associations between diabetes mellitus complications and some of the modifiable factors, including alcohol drinking, physical inactivity, and overweight. Clinicians and diabetes mellitus prevention programs should consider these modifiable factors to prevent chronic complications.