Background: Diabetes mellitus (DM) is a major growing health problem all over the world and especially for the low income countries. Therefore, sociological, clinical and disease factors that affect the disease outcome should be considered when managing DM patients.Objective: We aimed at determining the factors that were associated with in-hospital mortality in patients with diabetes mellitus at Kenyatta National Hospital from 2016 to 2020.Methods: We examined retrospective data from medical records of diabetes patients (n = 323, 48.3% males and 51.7% females) above 12 years admitted into the hospital from 2016 – 2020. Multivariable logistic regression analyses was performed to identify factors associated with in-hospital mortality.Results: Multivariable analysis showed that the odds for mortality were significantly high in those of age above 50 years (odds ratio 26.02, 95% confidence interval 9.54–70.92, p-value < 0.001), with unspecified DM type (OR 6.85, 95%CI 1.23–38.20, p = 0.028), DM type II (OR 3.00, 95%CI 1.35–6.67, p = 0.007), and hypertension (OR 2.94, 95%CI 1.47–5.88, p = 0.002), and nephropathy (OR 2.23 95%CI 1.14–4.38, p < 0.001). Other factors positively associated with in-hospital mortality included cardiovascular diseases, complication of diabetes ketoacidosis, oral hypoglycemic agents, soluble insulin, anti-hypertensives and antibiotics.Conclusion: Overall, the findings of this study suggest that advanced age, DM type II or unspecified type of DM, hypertension and nephropathy are the main drivers of mortality for patients with diabetes mellitus at Kenyatta National Hospital.