Objectives: We sought to evaluate the impact of post-primary percutaneous coronary intervention (PCI) Thrombolysis In Myocardial Infarction (TIMI) flow grades in the infarct-related artery (IRA) in patients with ST-segment elevation myocardial infarction (STEMI) and cardiogenic shock. Background: The clinical implications and correlates of post-procedural TIMI flow grades in patients with STEMI and cardiogenic shock treated with primary PCI have not been elucidated. Methods: We evaluated 4,731 STEMI patients with cardiogenic shock undergoing primary PCI at 567 hospitals participating in the American College of Cardiology-National Cardiovascular Database CathPCI Registry to determine the association of post-procedural TIMI flow grades 0 to 2 with in-hospital outcomes. Results: Post-PCI TIMI flow grades 0 to 2 in the IRA were present in 14.7% of patients. Compared with patients with TIMI flow grade 3, those with TIMI flow grades 0 to 2 were more likely to undergo coronary artery bypass graft surgery after PCI (20% vs. 5.4%), and develop renal failure (10.1% vs. 5.1%), cardiac tamponade (1.0% vs. 0.5%), and bleeding requiring blood transfusion (35.2% vs. 21.6%). Unadjusted mortality was more than 2-fold higher with TIMI flow grades 0 to 2 versus TIMI flow grade 3 (63% vs. 27%). There was a graded inverse relationship with TIMI flow in the IRA and the adjusted mortality (odds ratio [OR] for TIMI flow grades 0/1: 5.47 [95% confidence interval (CI): 4.13 to 7.24] and for TIMI flow grade 2: 2.63 [95% CI: 2.02 to 3.42] compared with TIMI flow grade 3). Our study also identified factors associated with post-PCI TIMI flow grades 0 to 2. Conclusions: Lack of procedural success (post-PCI TIMI flow grades 0 to 2 in the IRA) after primary PCI for STEMI among patients with cardiogenic shock is associated with a much higher risk of mortality compared with the risk for patients with normal post-PCI TIMI flow grade 3. © 2009 American College of Cardiology Foundation.