Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndrome (ACS). Recent data suggest a harmful association of dual antiplatelet therapy compared with single antiplatelet therapy following SCAD. This study investigated independent predictors of major adverse cardiovascular events (MACEs) and recurrence in patients with SCAD.This multicentre cohort study involving 23 Australian and New Zealand sites included patients aged ≥18 years with an ACS due to SCAD confirmed on core laboratory adjudication. Multivariable Cox proportional hazard models analysed predictors for the primary MACE outcome.Among 586 patients, 505 (150 prospective, 355 retrospective) with SCAD confirmed by core laboratory adjudication, mean age was 52.2 ± 10.6 years, 88.6% were female, and 74.5% were Caucasian. At long-term follow-up (median 21 months), MACE and SCAD recurrence occurred in 8.6% and 3.6% of patients, respectively. Oral anticoagulation on discharge [adjusted hazard ratio (aHR) 3.8, 95% confidence interval (CI) 1.6-9.3, P = .003], ticagrelor combined with aspirin (aHR 1.8, 95% CI 1.04-3.2, P = .037), fibromuscular dysplasia (aHR 2.2, 95% CI 1.05-4.5, P = .037), and history of stroke (aHR 3.8, 95% CI 1.2-12.2, P = .03) were independently associated with higher MACE. Fibromuscular dysplasia (aHR 3.9, 95% CI 1.5-26.5, P = .01), ticagrelor combined with aspirin (aHR 2.6, 95% CI 2.1-5.3, P = .01), and history of stroke (aHR 6.2, 95% CI 1.8-9.5, P = .01) were also associated with higher SCAD recurrence.The findings support the hypothesis that SCAD is primarily caused by intramural bleeding, with a harmful association of more potent antiplatelet therapy and anticoagulation with adverse cardiovascular outcomes.