Expanding the high-dose influenza vaccine recommendation to include middle-aged adults with chronic health conditions may make economic sense and save lives. The findings may justify for clinical trials of the high-dose and new recombinant trivalent influenza vaccines in 50- to 64-year-old adults with chronic illnesses, such as heart or lung disease, diabetes, or cancer, to determine if they do provide considerably better protection than the currently recommended standard dose quadrivalent vaccine.