BACKGROUND: Studies addressing patients with type 2 myocardial infarction and myocardial injury, including the impact of using high-sensitivity (hs) cardiac troponin (cTn) assays on their incidence are needed. METHODS: Ours is a prospective, observational US cohort study. Consecutive emergency department patients with serial cTnI measurements were studied. Outcomes included 180-day mortality and major adverse cardiac events, including 2-year follow-up for those with myonecrosis. RESULTS: Among 1640 patients, using a contemporary cTnI assay, 30% (n = 497) had >/=1 cTnI >99(th) percentile, with 4.7% (n = 77), 8.5% (n = 140), and 17% (n = 280) classified as type 1 myocardial infarction, type 2 myocardial infarction, and myocardial injury, respectively. Compared with patients without myonecrosis, 180-day mortality was higher for type 2 myocardial infarction (4% vs 13%, P < .0001) (adjusted hazard ratio 2.7; 95% confidence interval, 1.6-4.8; P = .0005) and myocardial injury (4% vs 11%, P < .0001) (adjusted hazard ratio 1.8; 95% confidence interval, 1.1-3.0; P = .02), both with mortality >20% at 2 years. Predictors of 2-year mortality for type 2 myocardial infarction included age, congestive heart failure, and beta-blockers. Relative to the contemporary cTnI assay, hs-cTnI had less myonecrosis (30% vs 26%, P = .003) and acute myocardial infarction (13.2% vs 10.8%, P = .032), including fewer type 2 myocardial infarctions (8.5% vs 6.3, P = .01), with no difference in myocardial injury (17% vs 15%, P = .1). CONCLUSIONS: cTnI increases are encountered in approximately a third of patients, the majority due to nonatherothrombotic conditions. Compared with patients without myonecrosis, type 2 myocardial infarction and myocardial injury have worse short-term outcomes, with mortality rates >20% at 2 years. hs-cTnI assay does not lead to more myocardial injury or infarction.