Abstract Aims Little is known about the outcomes and processes of care of patients with non-ST-segment myocardial infarction (NSTEMI) who present with ‘polyvascular’ disease. Methods and results We analysed 287 279 NSTEMI patients using the Myocardial Ischaemia National Audit Project registry. Clinical characteristics and outcomes were analysed according to history of affected vascular bed—coronary artery disease (CAD), cerebrovascular disease (CeVD), and peripheral vascular disease (PVD)—with comparison to a historically disease-free control group, comprising 167 947 patients (59%). After adjusting for demographics and management, polyvascular disease was associated with increased likelihood of major adverse cardiovascular events (MACEs) [CAD odds ratio (OR): 1.06; 95% confidence interval (CI): 1.01–1.12; P = 0.02] (CeVD OR: 1.19; 95% CI: 1.12–1.27; P < 0.001) (PVD OR: 1.22; 95% CI: 1.13–1.33; P < 0.001) and in-hospital mortality (CeVD OR: 1.24; 95% CI: 1.16–1.32; P < 0.001) (PVD OR: 1.33; 95% CI: 1.21–1.46; P < 0.001). Patients without vascular disease were less frequently discharged on statins (PVD 88%, CeVD 86%, CAD 90%, and control 78%), and those with moderate [ejection fraction (EF) 30–49%] or severe left ventricular systolic dysfunction (EF < 30%) were less frequently discharged on angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) (CAD 82%, CeVD 77%, PVD 77%, and control 74%). Patients with polyvascular disease were less likely to be discharged on dual antiplatelet therapy (DAPT) (PVD 78%, CeVD 77%, CAD 80%, and control 87%). Conclusion Polyvascular disease patients had a higher incidence of in-hospital mortality and MACEs. Patients with no history of vascular disease were less likely to receive statins or ACE inhibitors/ARBs, but more likely to receive DAPT.