Background: Thrombocytopenia following percutaneous coronary intervention (PCI) is an underappreciated condition that is often clinically challenging. There are no guidelines on the management of patients with this condition. Objective: To review recent data in etiologies, risk factors, prevention, management, and prognostic implications of thrombocytopenia following PCI. Evidence Acquisition: Search of MEDLINE, EMBASE, the Cochrane Database, and Google Scholar using the term thrombocytopenia + PCI and other relevant keywords to identify systematic reviews, clinical trials, cohort studies, case series, and case reports. The review was limited to English-language articles published between January 1980 and June 2009. Articles on patients with baseline thrombocytopenia prior to PCI were excluded. Evidence Synthesis: Thrombocytopenia is not infrequent following PCI. The typical patient with post-PCI thrombocytopenia is on multiple therapies that can potentially cause a decrease in the platelet count. Identification of the cause is critical because management of the condition varies significantly based on the etiology. The severity of the thrombocytopenia also determines the clinical management of the patient. Several observational studies have demonstrated the adverse prognostic impact of the complication on clinical outcomes and have identified risk factors. Conclusions: Judicious use of therapies that can cause thrombocytopenia, efficient detection of the cause of the decrease in platelet count, and appropriate management of the condition can potentially improve the quality of care and outcomes following PCI. Further research into risk factors that predispose post-PCI patients to developing thrombocytopenia is warranted.