Lower limb amputation (LLA) is frequently performed for advanced vascular disease and diabetes and is associated with substantial morbidity and mortality. Contemporary nationwide data from Sweden on survival following first-time LLA have been limited.To investigate national and regional trends in survival time, mortality rates, and associations with amputation level, demographic factors, and comorbidities among all adults undergoing a first LLA in Sweden between 2008 and 2017.This national observational cohort study included all individuals ≥18 years experiencing a first LLA (n = 16,757), identified through the Swedish National Inpatient Register and linked to the Cause of Death Register and socioeconomic data. Ten matched controls per case (n = 165,555) were selected by age, sex, region, and calendar year. Survival was assessed using Cox proportional hazards models, adjusted for demographics, socioeconomic status, comorbidities, and region. Outcomes included 30-day, 1-year, 3-year, and 5-year survival, median survival, and cause-specific mortality.Mortality was significantly higher after LLA compared with controls (adjusted HR (aHR) 3.32–3.69 across amputation levels). Median survival was 1.8 years among amputees versus 8.3 years in controls, and 5-year survival was 24.3% versus 66.2%. High proximal amputations had the poorest outcomes (median 1.0 year; 5-year survival 17.3%). Comorbidities markedly influenced mortality; chronic kidney disease (aHR 1.70), heart failure (1.44), dementia (1.42), and cancer (1.64) were strongest predictors. Diabetes was highly prevalent and associated with increased risk (aHR 1.21). Younger individuals had the highest relative mortality compared with matched controls. Vascular disease and diabetes dominated causes of death among amputees, contrasting with cancer and dementia in controls. Regional differences were modest but significant in several counties.LLA remains a strong marker of advanced systemic disease, and survival varies by amputation level, age, comorbidity burden, and socioeconomic factors. Despite advances in vascular and metabolic care, mortality remains high.In Sweden, first-time LLA is associated with markedly reduced survival, particularly for high proximal amputations and people with severe comorbidities. These findings highlight the need for intensified preventive vascular care, multidisciplinary perioperative management, and targeted rehabilitation strategies.