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Measures for pay-for-performance and public reporting programs may be based on clinical practice guidelines. The impact of guideline changes over time—and whether evolving clinical evidence can render measures based on prior guidelines misleading—is not known.To assess the impact of using different percutaneous coronary intervention (PCI) guidelines when evaluating whether PCI was indicated.PCIs from the National Cardiovascular Data Registry's CathPCI registry performed in 2003–2004 were categorized into indication classes (Class I, IIa, IIb, III), using 2001 American College of Cardiology/American Heart Association guidelines for PCI, the guidelines available at the time of the procedures. The same procedures were recategorized using 2005 guidelines, which reflect the best evidence available to clinicians at the time of PCI. Procedures unable to be categorized were labeled as “Not Certain.”Patients undergoing PCI for stable or unstable angina in 394 hospitals.Number of procedures changing classification categories using 2001 versus 2005 guidelines.A total of 345,779 PCIs were evaluated. Applying 2001 guidelines, 47.9% had Class I indications; 33.3% Class IIa; 5.9% Class IIb; 3.7% Class III; and 9.2% Not Certain. Applying 2005 guidelines to the same procedures, 25.1% had Class I indications; 57.5% Class IIa; 5.5% Class IIb; 3.7% Class III; and 8.3% Not Certain; 41.1% of procedures changed the classification overall.The changes in guidelines resulted in a marked shift in whether PCIs done in 2003–2004 were considered indicated. Guideline-based performance measures should be carefully evaluated before implementation to avoid incorrect assessments of quality of care.