What is already known about this topic? Two 2-dose mRNA COVID-19 vaccines (from Pfizer-BioNTech and Moderna) and a 1-dose viral vector vaccine (from Janssen [Johnson & Johnson]) are currently used in the United States. What is added by this report? Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization during March 11-August 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%). What are the implications for public health practice? Although these real-world data suggest some variation in levels of protection by vaccine, all FDA-approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization.