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Introduction: Mechanical ventilation is the most common intervention for patients with respiratory failure in the intensive care unit. There is limited data from African countries, including Ethiopia on time to death and its predictors among patients on mechanical ventilators. Therefore, this study aimed to assess time to death and its predictors among adult patients on mechanical ventilation admitted in comprehensive specialized hospitals in West Amhara, Ethiopia., Methods: An institutional-based retrospective follow-up study was conducted from January 1, 2020, to December 31, 2022. A simple random sampling was used to select a total of 391 patients' charts. Data were collected using data the extraction tool, entered into Epi-data version 4.6.0, and exported to STATA version 14 for analysis. Kaplan-Meier failure curve and the log-rank test were fitted to explore the survival difference among groups. The Cox regression model was fitted, and variables with a p-value < 0.25 in the bivariable Cox regression were candidates for the multivariable analysis. In the multivariable Cox proportional hazard regression, an adjusted hazard ratio with 95% confidence intervals were reported to declare the strength of association between mortality and predictors when a p value is < 0.05., Results: A total of 391 mechanically ventilated patients were followed for 4098 days at risk. The overall mortality of patients on mechanical ventilation admitted to the intensive care units was 62.2%, with a median time to death of 16 days (95% CI: 11, 22). Those patients who underwent tracheostomy procedure (AHR = 0.40, 95% CI: 0.20, 0.80), received cardio-pulmonary resuscitation (AHR = 8.78, 95% CI: 5.38, 14.35), being hypotensive (AHR = 2.96, 95% CI: 1.11, 7.87), and had a respiratory rate less than 12 (AHR = 2.74, 95% CI: 1.48, 5.07) were statistically significant predictors of time to death among mechanically ventilated patients., Conclusion: The mortality rate of patients on mechanical ventilation was found to be high and the time to death was short. Being cardiopulmonary resuscitated, hypotensive, and had lower respiratory rate were significant predictors of time to death, whereas patients who underwent tracheostomy was negatively associated with time to death. Tracheostomy is needed for patients who received longer mechanical ventilation, and healthcare providers should give a special attention for patients who are cardiopulmonary resuscitated, hypotensive, and have lower respiratory rate., (© 2024. The Author(s).)