Influenza activity started earlier than usual in the United States this season, with widespread influenza activity reported in 10 states by November 22, 2003. The predominant influenza viruses (A/Fujian/411/2002 [H3N2]-like viruses) circulating this season differ antigenically from the 2003-04 influenza A (H3N2) vaccine strain. A retrospective cohort study was conducted among workers at a Colorado hospital to provide preliminary data on the effectiveness of trivalent inactivated influenza vaccine (TIV) against influenza-like illness (ILI). This report summarizes the results of that study, which indicated that TIV had no or low effectiveness against ILI. However, additional studies are needed to evaluate the effectiveness of the 2003-04 vaccine against laboratory-confirmed influenza and influenza-related complications, including hospitalization and death. Influenza vaccine continues to be recommended, particularly for persons at increased risk for influenza-related complications, their household contacts, and health-care personnel.