["Addiction, EarlyView. ", "\nAbstract\n\nBackground and aims\nPeople with substance‐use disorders (SUDs) have increased mortality risk, yet Chilean estimates of SUD‐based mortality are scarce. This study aimed to quantify all‐cause and cause‐specific mortality following SUD treatment in Chile compared with the general population and assess variation across key clinical and demographic subgroups.\n\n\nDesign\nNational‐level registry‐based retrospective data linkage cohort study.\n\n\nSetting\nPublicly funded SUD psychosocial treatments offered by the Chilean National Drug Agency, linked with official national mortality records from 2010 to 2020.\n\n\nParticipants\n70064 adults aged 18–64 years (24% women, median age 35 at treatment entry) were followed after their first treatment episode until death or 31 December 2020.\n\n\nMeasurements\nPrimary outcome was all‐cause mortality. Secondary outcomes were cause‐specific mortality by the International Classification of Diseases, 10th revision, underlying and external causes. We estimated age–sex–calendar year directly standardized rates (DSR), and standardized mortality ratios (SMR) compared with the expected rate for the (sub)population. We also stratified rates and ratios by sex (men/women), attained age (18–29, 30–44, 45–59, 60+), setting (ambulatory/residential), primary substance (alcohol; illicit: predominantly cocaine paste base, marijuana and cocaine hydrochloride) and treatment compliance (not completed/completed). Additionally, we estimated rates and SMRs for underlying and external causes of mortality.\n\n\nFindings\nOver a median 4.9‐year follow‐up (353 826 person‐years), 2996 deaths occurred [DSR = 10.6, 95% confidence interval (CI) = 8.6–13.1]. Overall SMR was 3.65 (95% CI = 3.52–3.79). Excess risk was particularly pronounced for women (SMR = 5.57, 95% CI = 5.14–6.03), patients admitted due to alcohol use disorder (SMR = 4.59, 95% CI = 4.33–4.86), in residential care (SMR = 4.91, 95% CI = 4.45–5.42) and treatment noncompletion (SMR = 4.04, 95% CI = 3.85–4.24). Cause‐specific mortality revealed elevated external‐cause excess risk for SUD patients, including intentional self‐harm (SMR = 6.67, 95% CI = 6.05–7.36), unintentional injuries (SMR = 5.37, 95% CI = 4.79–6.02) and assaults (SMR = 4.98, 95% CI = 4.16–5.96). Notable excess risk was also observed for non‐external mortality causes: digestive system (SMR = 8.20, 95% CI = 7.62–8.83), symptoms and signs (SMR = 5.18, 95% CI = 4.29–6.26) and respiratory diseases (SMR = 5.18, 95% CI = 4.47–5.99) were greater than expected.\n\n\nConclusions\nIn Chile, patients with a history of publicly funded substance‐use disorder treatment appear to have an all‐cause mortality up to 3.7 times higher than the general population, driven predominantly by digestive and respiratory causes, as well as self‐harm, unintentional injuries and assaults.\n\n"]