We explored nonsteroidal anti-inflammatory drug (NSAID) and aspirin (ASA) use and mortality in the U.S. Department of Health and Human Services' registry of 683 adult and 838 pediatric critically ill pandemic 2009 H1N1 influenza (pH1N1) patients. Among adults, 88 (12.9%) and 101 (14.8%) reported pre-admission use of an NSAID and ASA, respectively; mortality was similar (23-24%) regardless of NSAID or ASA use. Mortality among 89 pediatric NSAID users and 749 nonusers did not differ significantly (10.1% and 8.8%, respectively). One of 16 pediatric ASA users died. Among pediatric patients, the adjusted relative risk estimate for NSAID use and 90-day mortality was higher when influenza vaccination was included in the model (risk ratio [RR] = 1.5; 95% confidence interval, 0.7-3.2), although not statistically significant. Among adults, RR estimates did not change appreciably after adjusting for age, sex, health status, or vaccine status. We found no compelling evidence that NSAID or ASA use influenced mortality in severe pH1N1.