Objectives: The spread of severe acute respiratory syndrome coronavirus 2 in Ethiopia is below par understood and to date has been poorly characterized by a lower number of confirmed cases and deaths to other regions of the sub-Sahara African including Ethiopia. Timely and effective predictors for inpatient mortality rate were crucial for improving the management of hospitalized cases. This study aimed to assessed predictors for inpatient mortality of COVID-19 hospitalized adult patients in two diagnosed and treatment centers, North West Ethiopia. Methods: A facility-based retrospective cohort study was conducted among COVID-19 adult admitted cases in two treatment centers, Northwest Ethiopia, from 1 October 2020 to 30 December 2020. Data from the records of children were extracted using a standardized checklist. Epi-Data version 3.2 was used for data entry, and Stata version 14 was used for analysis. Bi-variable and multivariable Cox regression analyses were conducted to identify predictors of mortality. Finally, variables with P < 0.05 were a significant predictor of inpatient mortality. Result: The mean (±standard deviation) age of participant cases was 48.6 (±18.8) years. The median (±interquartile range) time for death reported after was 13 (±6) days. The overall incidence rate inpatient mortality rate was determined as 1.8 (95% confidence interval: 1.72, 2.15) per100 person per days of observation. Cases at baseline age ⩾ 61 years (adjusted hazard ratio = 1.56; 95% confidence interval: 1.3, 2.4), being male gender (adjusted hazard ratio = 1.9; 95% CI: 2.1, 8.6), admission with comorbidity (adjusted hazard ratio: 4.4, 95% confidence interval: 2.3, 8.4), and decreased neutrophil count ⩽ 65 103/uL at (P < 0.03) were independent predictors for inpatient mortality. Conclusion: In general, 72.4% of COVID-19 inpatient deaths were occurred within 2 weeks after admission. The mortality risk factors for severe patients identified in this study using a multivariate Cox regression model included elderly age (⩾60 years), being male, baseline comorbidity, and neutrophil count ⩽65 103/uL were associated with inpatient mortality.