Although computerized physician order entry (CPOE) prescribing systems are commonly believed to improve patient safety and outcomes, this single-hospital study discovered increased mortality rates after implementation. Investigators retrospectively analyzed several variables in the 13 months before and 5 months following implementation. Even after adjustment for mortality variables, CPOE was independently associated with 3.28 greater odds for mortality. Additional findings include the workflow challenges and increased time required to enter orders compared with traditional handwritten practices. Given the national interest in CPOE, these findings should reinforce the understanding that CPOE is a tool rather than a solution for patient safety and that appropriate vigilance in implementation is necessary.