Influenza is a major cause of respiratory infection and has a high mortality rate in the elderly. Neuraminidase (NA) on the surface of the influenza virus and bacterial trypsin-like proteases (TLP) play key roles in influenza virus infections. We investigated the effects of oral care on influenza, evaluating in particular the activities of NA and TLP in saliva, as they may contribute to an increased risk of infection with influenza. One hundred ninety elderly patients who visited day care service facilities once a week were randomly assigned to either a professional oral care group or to an own oral care group as the control group. Nine individuals in the control group and one person in the professional oral care group were diagnosed with influenza during the follow-up period. The relative risk of developing influenza while under professional oral care compared to that in the control group was 0.1 (95% CI 0.01-0.81, p=0.008). Significant decreases in numbers of salivary anaerobic bacterial CFUs, and NA and TLP levels were observed in the professional oral care group compared to that in the control group (p<0.01). This study suggests that maintenance of oral hygiene is effective in the prevention of influenza in the elderly.