Purpose: Under Medicare's Coverage with Evidence Development policy, positron emission tomography (PET)/computed tomography (CT) and PET became covered services for previously noncovered cancer indications if prospective registry data were collected. The National Oncologic PET Registry (NOPR) was developed to meet these coverage requirements and to assess how PET affects care decisions. Methods: The NOPR collected questionnaire data from referring physicians on intended patient management before and after PET. After 1 year, the cohort included data from 22,975 studies (83.7% PET/CT) from 1,178 centers. The numbers of scans performed for diagnosis of suspected cancer (or unknown primary cancer), initial cancer staging, restaging, and suspected cancer recurrence were approximately equal. Prostatic, pancreatic and ovarian cancers represented approximately 30% of cases. Results: If PET data were not available, the most common pre-PET plan would have been other imaging. In these patients, the post-PET strategies changed to watching in 37% and treatment in 48%. In patients with planned biopsy before PET, biopsy was avoided in approximately 70%. If the pre-PET strategy was treatment, the post-PET strategy involved a major change in type in 8.7% and goal in 5.6%. When intended management was classified as either treatment or nontreatment, the post-PET plan was three-fold more likely to lead to treatment than nontreatment (28.3% v 8.2%; odds ratio = 3.4; 95% CI, 3.2 to 3.6). Overall, physicians changed their intended management in 36.5% (95% CI, 35.9 to 37.2) of cases after PET. Conclusion: This large, prospective, nationally representative registry of elderly cancer patients found that physicians often change their intended management on the basis of PET scan results across the full spectrum of its potential uses.