Objectives: We sought to determine the occurrence, predictors, and prognostic impact of post-percutaneous coronary intervention (post-PCI) thrombocytopenia on an unselected real-world patient population. Background: Thrombocytopenia after PCI has been shown to portend worse prognosis in clinical trials. The significance of post-PCI thrombocytopenia has not previously been examined outside the clinical trial setting. Methods: The study cohort consisted of 1,302 consecutive patients with normal baseline platelet count (150 × 10 9/L). Post-PCI thrombocytopenia was defined as nadir platelet count <100 × 10 9/L or a drop >50% from baseline. The primary outcomes were in-hospital and 6-month rates of death and major adverse cardiovascular events (MACE), and the secondary outcomes were bleeding, need for blood transfusion, and length of hospital stay. Logistic regression was performed to identify independent predictors. Results: Post-PCI thrombocytopenia developed in 41 patients (occurrence 3.1%). Independent predictors were baseline creatinine clearance (odds ratio [OR] 1.02 for every unit decrease, 95% confidence interval [CI] 1.01-1.03, P = 0.001), failed PCI (OR 3.8, CI 1.6-9.4, P = 0.003), and use of intraaortic balloon pump (OR 2.8, CI 1.1-6.8, P = 0.024). All study outcomes were significantly higher in patients with post-PCI thrombocytopenia. Post-PCI thrombocytopenia independently predicted MACE at 6 months (hazard ratio 2.7, CI 1.3-5.5, P = 0.0069) and all the secondary outcomes. Conclusions: Post-PCI thrombocytopenia occurred in 3.1% of patients in an unselected real-world population and carried a significant detrimental impact on prognosis. Failed PCI was the strongest correlate identified.