Telephone nurse triage lines, such as the Centers for Disease Control and Prevention’s (CDC) Flu on Call®, a national nurse triage line, may help reduce the surge in demand for health care during an influenza pandemic by triaging callers, providing advice about clinical care and information about the pandemic, and providing access to prescription antiviral medication. We developed a Call Volume Projection Tool to estimate national call volume to Flu on Call® during an influenza pandemic. The tool incorporates 2 influenza clinical attack rates (20% and 30%), 4 different levels of pandemic severity, and different initial “seed numbers” of cases (10 or 100), and it allows variation in which week the nurse triage line opens. The tool calculates call volume by using call-to-hospitalization ratios based on pandemic severity. We derived data on nurse triage line calls and call-to-hospitalization ratios from experience with the 2009 Minnesota FluLine nurse triage line. Assuming a 20% clinical attack rate and a case hospitalization rate of 0.8% to 1.5% (1968-like pandemic severity), we estimated the nationwide number of calls during the peak week of the pandemic to range from 1,551,882 to 3,523,902. Assuming a more severe 1957-like pandemic (case hospitalization rate = 1.5% to 3.0%), the national number of calls during the peak week of the pandemic ranged from 2,909,778 to 7,047,804. These results will aid in planning and developing nurse triage lines at both the national and state levels for use during a future influenza pandemic.