We compared the clinical characteristics and outcomes of young patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) versus obstructive disease (myocardial infarction due to coronary artery disease MI-CAD) and among patients with MINOCA by sex and subtype. Between 2008 and 2012, VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) prospectively enrolled acute myocardial infarction patients aged 18 to 55 years in 103 hospitals at a 2:1 ratio of women to men. Using an angiographically driven taxonomy, we defined patients as having MI-CAD if there was revascularization or plaque ≥50% and as having MINOCA if there was <50% obstruction or a nonplaque mechanism. Patients who did not have an angiogram or who received thrombolytics before an angiogram were excluded. Outcomes included 1- and 12-month mortality and functional (Seattle Angina Questionnaire SAQ) and psychosocial status. Of 2690 patients undergoing angiography, 2374 (88.4%) had MI-CAD, 299 (11.1%) had MINOCA, and 17 (0.6%) remained unclassified. Women had 5 times higher odds of having MINOCA than men (14.9% versus 3.5%; odds ratio: 4.84; 95% confidence interval, 3.29-7.13). MINOCA patients were more likely to be without traditional cardiac risk factors (8.7% versus 1.3%; <0.001) but more predisposed to hypercoaguable states than MI-CAD patients (3.0% versus 1.3%; =0.036). Women with MI-CAD were more likely than those with MINOCA to be menopausal (55.2% versus 41.2%; <0.001) or to have a history of gestational diabetes mellitus (16.8% versus 11.0%; =0.028). The MINOCA mechanisms varied: a nonplaque mechanism was identified for 75 patients (25.1%), and their clinical profiles and management also varied. One- and 12-month mortality with MINOCA and MI-CAD was similar (1-month: 1.1% and 1.7% =0.43; 12-month: 0.6% and 2.3% =0.68, respectively), as was adjusted 12-month SAQ quality of life (76.5 versus 73.5, respectively; =0.06). Young patients with MINOCA were more likely women, had a heterogeneous mechanistic profile, and had clinical outcomes that were comparable to those of MI-CAD patients. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00597922.