Background: The management of chronic thoracic aortic aneurysms includes conservative management, watchful waiting, endovascular stent grafting and open surgical replacement. The Effective Treatments for Thoracic Aortic Aneurysms (ETTAA) study investigates timing and intervention choice. Objective: To describe pre- and post-intervention management of and outcomes for chronic thoracic aortic aneurysms. Design: A systematic review of intervention effects; a Delphi study of 360 case scenarios based on aneurysm size, location, age, operative risk and connective tissue disorders; and a prospective cohort study of growth, clinical outcomes, costs and quality of life. Setting: Thirty NHS vascular/cardiothoracic units. Participants: Patients aged > 17 years who had existing or new aneurysms of ≥ 4 cm in diameter in the arch, descending or thoracoabdominal aorta. Interventions: Endovascular stent grafting and open surgical replacement. Main outcomes: Pre-intervention aneurysm growth, pre-/post-intervention survival, clinical events, readmissions and quality of life; and descriptive statistics for costs and quality-adjusted life-years over 12 months and value of information using a propensity score-matched subsample. Results: The review identified five comparative cohort studies (endovascular stent grafting patients, n = 3955; open surgical replacement patients, n = 21,197). Pooled short-term all-cause mortality favoured endovascular stent grafting (odds ratio 0.71, 95% confidence interval 0.51 to 0.98; no heterogeneity). Data on survival beyond 30 days were mixed. Fewer short-term complications were reported with endovascular stent grafting. The Delphi study included 20 experts (13 centres). For patients with aneurysms of ≤ 6.0 cm in diameter, watchful waiting was preferred. For patients with aneurysms of > 6.0 cm, open surgical replacement was preferred in the arch, except for elderly or high-risk patients, and in the descending aorta if patients had connective tissue disorders. Otherwise endovascular stent grafting was preferred. Between 2014 and 2018, 886 patients were recruited (watchful waiting, n = 489; conservative management, n = 112; endovascular stent grafting, n = 150; open surgical replacement, n = 135). Pre-intervention death rate was 8.6% per patient-year; 49.6% of deaths were aneurysm related. Death rates were higher for women (hazard ratio 1.79, 95% confidence interval 1.25 to 2.57; p = 0.001) and older patients (age 61–70 years: hazard ratio 2.50, 95% confidence interval 0.76 to 5.43; age 71–80 years: hazard ratio 3.49, 95% confidence interval 1.26 to 9.66; age > 80 years: hazard ratio 7.01, 95% confidence interval 2.50 to 19.62; all compared with age < 60 years, p < 0.001) and per 1-cm increase in diameter (hazard ratio 1.90, 95% confidence interval 1.65 to 2.18; p = 0.001). The results were similar for aneurysm-related deaths. Decline per year in quality of life was greater for older patients (additional change –0.013 per decade increase in age, 95% confidence interval –0.019 to –0.007; p < 0.001) and smokers (additional change for ex-smokers compared with non-smokers 0.003, 95% confidence interval –0.026 to 0.032; additional change for current smokers compared with non-smokers –0.034, 95% confidence interval –0.057 to –0.01; p = 0.004). At the time of intervention, endovascular stent grafting patients were older (age difference 7.1 years; 95% confidence interval 4.7 to 9.5 years; p < 0.001) and more likely to be smokers (75.8% vs. 66.4%; p = 0.080), have valve disease (89.9% vs. 71.6%; p < 0.0001), have chronic obstructive pulmonary disease (21.3% vs. 13.3%; p = 0.087), be at New York Heart Association stage III/IV (22.3% vs. 16.0%; p = 0.217), have lower levels of haemoglobin (difference –6.8 g/l, 95% confidence interval –11.2 to –2.4 g/l; p = 0.003) and take statins (69.3% vs. 42.2%; p < 0.0001). Ten (6.7%) endovascular stent grafting and 15 (11.1%) open surgical replacement patients died within 30 days of the procedure (p = 0.2107). One-year overall survival was 82.5% (95% confidence interval 75.2% to 87.8%) after endovascular stent grafting and 79.3% (95% confidence interval 71.1% to 85.4%) after open surgical replacement. Variables affecting survival were aneurysm site, age, New York Heart Association stage and time waiting for procedure. For endovascular stent grafting, utility decreased slightly, by –0.017 (95% confidence interval –0.062 to 0.027), in the first 6 weeks. For open surgical replacement, there was a substantial decrease of –0.160 (95% confidence interval –0.199 to –0.121; p < 0.001) up to 6 weeks after the procedure. Over 12 months endovascular stent grafting was less costly, with higher quality-adjusted life-years. Formal economic analysis was unfeasible. Limitations: The study was limited by small numbers of patients receiving interventions and because only 53% of patients were suitable for both interventions. Conclusions: Small (4–6 cm) aneurysms require close observation. Larger (> 6 cm) aneurysms require intervention without delay. Endovascular stent grafting and open surgical replacement were successful for carefully selected patients, but cost comparisons were unfeasible. The choice of intervention is well established, but the timing of intervention remains challenging. Future work: Further research should include an analysis of the risk factors for growth/rupture and long-term outcomes. Trial registration: Current Controlled Trials ISRCTN04044627 and NCT02010892.