OBJECTIVES: The aim of this study was to determine the impact of invasive approaches and revascularization in patients with cocaine-associated non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND: The role of invasive approaches in cocaine-associated NSTEMI is uncertain. METHODS: This retrospective cohort study identified 3,735 patients with NSTEMI and history of cocaine use from the Nationwide Readmissions Database from 2016 to 2017. Invasive approaches were defined as coronary angiography, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). Revascularization was defined as PCI and CABG. The primary efficacy outcome was major adverse cardiac events (MACE), and the primary safety outcome was emergent revascularization. Nonadherence was identified using appropriate International Classification of Diseases-Tenth Revision codes. Two propensity-matched cohorts were generated (noninvasive vs. invasive and noninvasive vs. revascularization) through multivariate logistic regression. RESULTS: In the propensity score-matched cohorts, an invasive approach (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.56 to 0.92; p = 0.008) and revascularization (HR: 0.54; 95% CI: 0.40 to 0.73; p < 0.001) (compared with a noninvasive approach) were associated with a lower rate of MACE, without an increase in emergent revascularization. On stratification, PCI and CABG individually were associated with a lower rate of MACE. Emergent revascularization was increased with PCI (HR: 1.78; 95% CI: 1.12 to 2.81; p = 0.014) but not with CABG. Nonadherent patients after PCI and CABG did not have significant difference in rate of MACE. PCI in nonadherent patients was associated with an increase in emergent revascularization (HR: 4.45; 95% CI: 2.07 to 9.57; p < 0.001). CONCLUSIONS: Invasive approaches and revascularization for cocaine-associated NSTEMI are associated with lower morbidity. A history of medical nonadherence was not associated with a difference in morbidity but was associated with an increased risk for emergent revascularization with PCI.