The effects of more than a decade of national efforts dedicated to improve patient safety remain largely unclear. This study used the Medicare Patient Safety Monitoring System (MPSMS) database to assess national trends in adverse event rates between 2005 through 2011 for patients hospitalized with acute myocardial infarction, congestive heart failure, pneumonia, or conditions requiring surgery. The analysis included a large study sample with more than 60,000 patients across 4372 hospitals. The results show a significant decline in adverse event rates for acute myocardial infarction and congestive heart failure, translating to an estimated 81,000 in-hospital adverse events averted in 2010–2011. However, there were no measurable overall improvements for patients admitted with pneumonia or surgical conditions. Some events, such as pressure ulcers in surgical patients, actually increased despite considerable national attention to these problems. This study suggests that national patient safety initiatives have led to real progress in some areas but have not created across-the-board improvements.