The Patient-Reported Outcomes Measurement Information System (PROMIS™) initiative aims to develop and evaluate efficient, flexible, and precise measurement tools for patient-reported outcomes (PROs) in clinical research and healthcare settings. This article reports on the first large-scale testing of PROMIS items from 2005 to 2008, involving 14 item pools tested in the U.S. general population and clinical groups. Using item response theory, 11 item banks were calibrated, covering physical, mental, and social health, along with a global health scale. Short forms from each bank were developed and compared to the overall bank and legacy measures, demonstrating good reliability and construct validity. The PROMIS item banks and their short forms provide reliable and precise measures of generic symptoms and functional reports, comparable to legacy instruments. Further testing will validate and test PROMIS items in diverse clinical populations.The Patient-Reported Outcomes Measurement Information System (PROMIS™) initiative aims to develop and evaluate efficient, flexible, and precise measurement tools for patient-reported outcomes (PROs) in clinical research and healthcare settings. This article reports on the first large-scale testing of PROMIS items from 2005 to 2008, involving 14 item pools tested in the U.S. general population and clinical groups. Using item response theory, 11 item banks were calibrated, covering physical, mental, and social health, along with a global health scale. Short forms from each bank were developed and compared to the overall bank and legacy measures, demonstrating good reliability and construct validity. The PROMIS item banks and their short forms provide reliable and precise measures of generic symptoms and functional reports, comparable to legacy instruments. Further testing will validate and test PROMIS items in diverse clinical populations.