Approximately 150 million Americans lived in large metropolitan jurisdictions in 2013. About 1 in 7 Americans is served by a member of the Big Cities Health Coalition (BCHC), a group of 20 of the largest local health departments (LHDs) in the United States. In this brief, we describe the organizational characteristics of the country's largest health departments, including those that form the BCHC, and quantify the differences and variation among them. We conducted secondary analyses of the 2013 National Association of County & City Health Officials Profile, specifically characterizing differences between BCHC members and other large LHDs. The data set contained 2000 LHDs that responded to National Association of County & City Health Officials' 2013 Profile. While LHDs serving 500,000 or more people account for only 5% of all LHDs, they covered 50% of the US population in 2013. The BCHC members served approximately 46 million people. The BCHC LHDs had a greater number of staff, larger budgets, and were more involved in policy than their larger peers.