Background: Influenza related morbidity and mortality disproportionately impacts older adults. The serologic response to vaccine is diminished in older adults; however, high dose inactivated influenza vaccine (HD IIV) has shown improved rates of seroconversion compared to standard dose (SD IIV). We hypothesize this may be due to the superior ability of high dose vaccine to activate T follicular helper (Tfh) cells and provide B cell dependent T cell help.Methods: We measured peripheral Tfh (pTfh) activation in 50 community dwelling adults 65 years or older who were randomly assigned to receive either the HD IIV or SD IIV.Results: The HD vaccination elicited significantly higher levels of ICOS expression on pTfh cells, at day 7 compared to SD vaccination (p = 0.02). The magnitude of the increase in ICOS+ pTfh cells from baseline to day 7 was predictive of seroconversion for both influenza A and B vaccination.Conclusion: Strong Tfh activation in response to influenza vaccination forecasts successful seroconversion in older adults, and HD IIV elicits greater Tfh activation than SD fly. Future vaccine studies should focus on ways to further optimize the Tfh response. (C) 2016 Elsevier Ltd. All rights reserved.