Background: Due to a single infectious pathogen, tuberculosis (TB) is the world's second-greatest cause of mortality. The majority of TB deaths happen during the intensive phase of treatment. The purpose of this study is to determine the incidence and predictors of in-hospital mortality in adult TB patients. Method: A 4 year retrospective follow-up study was conducted among 200 admitted adult TB patients at the university of Gondar hospital from September 1, 2017 to September 30, 202l. The Cox proportional hazards model was used to calculate the hazard ratios (HR). The Kaplan-Meier method was used to compute survival rates. Cox regression models were used to determine the predictors of mortality. Results: This study enrolled 200 adult TB patients. Among these 60 (30%) died, 140 (70%) censored with overall incidence of death rate of 165 (95 percent CI: 128, 213)/10,000 days of observation. A multivariate Cox regression analysis revealed that patients with a low WBC count at baseline (AHR=3.16, 95% CI: 1.55, 6.41) and bedridden patients (AHR=3.49, 95% CI: 1.83, 6.66) independent predictors of in-hospital mortality among adult TB patients. Conclusions: This retrospective study found that hospital mortality among adult TB patients is high in public hospitals in northwest Ethiopia. Patients with a low WBC count and who were bedridden at the time of presentation were independent predictors of in-hospital mortality.