Background: While established clinical guidelines provide foundational recommendations for managing aortic dissection (AD), there is a significant lack of recent, large-scale evidence to definitively delineate optimal medical therapy, particularly concerning specific medication choices and dosages in the chronic period of the disease. Methods: Swedish National Patient Register and Cause of Death Register were used to identify new AD between 2006 and 2021. The impact of pre-dissection medications on survival was analysed. Landmark analysis of 10 year failure of medical therapy, aorta-related death and all-cause mortality was investigated with subgroup analysis of beta-blocker, antihypertensive and the role of adjunctive medications. All analyses controlled for age and sex. Results: A total of 12,223 patients were included, of which 4853 (39.7%) were females. Patients who were on metformin, an antiplatelet, statin or anticoagulant did not have a protective benefit to survival following AD, however metformin had a significant protective effect for 10 year failure of medical therapy (p = 0.00622). In patients with diagnosed diabetes, those on metformin also had a significant survival benefit (p = 0.0362). Non-selective beta-blockers had the poorest mortality compared to selective or alpha and beta-blockers (p = 0.089) though this wasn't significant for aortic death (p = 0.52) and a trend to more failure of medical therapy (p = 0.072). Being commenced on an anticoagulant and antiplatelet significantly increased all cause mortality while commencing a statin trended towards poorer all cause and aortic death. Conclusions: This is the largest analysed cohort focussing on optimal medical therapy for AD. The role of metformin having a protective aortic effects is demonstrated but requires more focussed investigation. Antihypertensive choice did not impact outcomes, though selective beta-blockers provide the best mortality and failure of medical therapy outcomes.