RATIONALE: Since the introduction of long-term oxygen treatment (LTOT) in COPD with chronic hypoxia, the proportion of women and the age of patients starting LTOT has increased markedly. We hypothesize that this might have led to shifts in the causes of death over time. OBJECTIVES: To test for time trends in cause-specific mortality in COPD with LTOT. METHODS: Patients starting LTOT for COPD in Sweden between 1 January 1987 and 31 December 2004 were included in a national prospective study and followed until withdrawal of LTOT, death or 31 December 2004. The primary endpoint was cause of death obtained from the National Causes of Death Register. MEASUREMENTS AND MAIN RESULTS: A total of 7,628 patients (53% women) were followed for a median of 1.7 years (range 0-18.0). No patient was lost to follow up and 5,457 patients died during the study. The crude overall mortality increased by 1.6% per year (95% confidence interval (CI), 0.9-2.2; P