Key Points Question What antiviral agents for treating seasonal influenza are associated with the most safety and best outcomes among healthy adults and children? Findings This network meta-analysis of 26 randomized clinical trials, including 11 897 patients, found that antiviral agents were associated with significantly greater efficacy than placebo in shortening the duration of influenza symptoms; zanamivir was associated with the shortest time to alleviation of influenza symptoms. Baloxavir was associated with a lower occurrence of influenza-related complications than other treatments. Meaning These findings suggest that zanamivir may be initiated as soon as possible for patients with influenza-like illness; in those who may be at high risk of developing influenza-related complications, baloxavir should be considered.