Background. Recipients of high-dose vs standard-dose influenza vaccines have fewer influenza illnesses. We evaluated the comparative effectiveness of high-dose vaccine in preventing postinfluenza deaths during 2012-2013 and 2013-2014, when influenza viruses and vaccines were similar. Methods. We identified Medicare beneficiaries aged = 65 years who received high-dose or standard-dose vaccines in community- located pharmacies offering both vaccines. The primary outcome was death in the 30 days following an inpatient or emergency department encounter listing an influenza International of Classification of Diseases, Ninth Revision, Clinical Modification code. Effectiveness was estimated by using multivariate Poisson regression models; effectiveness was allowed to vary by season. Results. We studied 1 039 645 recipients of high-dose and 1 683 264 recipients of standard-dose vaccines during 2012-2013, and 1 508 176 high-dose and 1 877 327 standard-dose recipients during 2013-2014. Vaccinees were well-balanced for medical conditions and indicators of frail health. Rates of postinfluenza death were 0.028 and 0.038/10 000 person-weeks in high-dose and standard-dose recipients, respectively. Comparative effectiveness was 24.0% (95% confidence interval [CI],.6%-42%); there was evidence of variation by season (P =.12). In 2012-2013, high-dose was 36.4% (95% CI, 9.0%-56%) more effective in reducing mortality; in 2013-2014, it was 2.5% (95% CI, -47% to 35%). Conclusions. High-dose vaccine was significantly more effective in preventing postinfluenza deaths in 2012-2013, when A(H3N2) circulation was common, but not in 2013-2014.