BackgroundCambodia was recently removed from the World Health Organization’s (WHO’s) top 30 high tuberculosis (TB) burden countries. However, Cambodia’s TB burden remains substantial, and the country is on the WHO’s new global TB watchlist. We aimed to examine the levels and trends in the fatal and non-fatal TB burden in Cambodia from 1990 to 2019, assessing progress towards the WHO End TB interim milestones, which aim to reduce TB incidence rate by 20% and TB deaths by 35% from 2015 to 2020.MethodsWe leveraged the Global Burden of Disease 2019 (GBD 2019) analytical framework to compute age- and sex-specific TB mortality and incidence by HIV status in Cambodia. We enumerated TB mortality utilizing a Bayesian hierarchical Cause of Death Ensemble modeling platform. We analyzed all available data sources, including prevalence surveys, population-based tuberculin surveys, and TB cause-specific mortality, to produce internally consistent estimates of incidence and mortality using a compartmental meta-regression tool (DisMod-MR 2.1). We further estimated the fraction of tuberculosis mortality among individuals without HIV coinfection attributable to the independent effects of alcohol use, smoking, and diabetes.ResultsIn 2019, there were 6500 (95% uncertainty interval 4830–8680) deaths due to all-form TB and 50.0 (43.8–57.8) thousand all-form TB incident cases in Cambodia. The corresponding age-standardized rates were 53.3 (39.9–69.4) per 100,000 population for mortality and 330.5 (289.0–378.6) per 100,000 population for incidence. From 2015 to 2019, the number of all-form TB deaths decreased by 11.8% (2.3–21.1), while the age-standardized all-form TB incidence rate decreased by 11.1% (6.3–15.6). Among individuals without HIV coinfection in 2019, alcohol use accounted for 28.1% (18.2–37.9) of TB deaths, smoking accounted for 27.0% (20.2–33.3), and diabetes accounted for 12.5% (7.1–19.0). Removing the combined effects of these risk factors would reduce all-form TB deaths by 54.2% (44.2–62.2).DiscussionDespite significant progress in reducing TB morbidity and mortality since 1990, Cambodia is not on track to achieve the 2020 WHO End TB interim milestones. Existing programs in Cambodia can benefit from liaising with risk factor control initiatives to accelerate progress toward eliminating TB in Cambodia.