Chronic low-grade inflammation (inflammaging) accompanies aging and is thought to be a key driver of age-related disease. Whether anti-inflammatory medications could be beneficial in helping to prolong healthspan is unclear. The aim of this study was to determine, in older individuals, the effect of aspirin on intrinsic capacity (IC), the WHO defined measure of heathy aging. The ASPirin in Reducing Events in the Elderly (ASPREE) trial randomized 19,114 community-dwelling individuals aged predominantly ≥70 years to daily low-dose aspirin (100mg) or placebo over five years. Four domains of IC were assessed regularly over the trial period: cognition (composite score across four tests), locomotion (gait speed), vitality (grip strength) and psychological well-being (CESD-10). IC was calculated as the arithmetic mean of four normalized and rescaled IC domains scores. At baseline, being older and a woman (56.4% of the sample) was associated with lower IC (p<0.001 for both). IC was negatively correlated with the frailty deficit accumulation index (r = – 0.57, p<0.001). Over a median 4.7-year follow-up period, IC declined to a similar extent in both men and women. Compared with placebo, aspirin treatment was associated with a faster decline in IC among women (β -0.06, 95% CI: -0.10, -0.01). For men, aspirin had no effect on IC (β -0.01, 95% CI: -0.05, 0.04). Additional adjustment for age, country, ethnicity and race did not modify these findings. Further work is needed to determine the mechanisms underpinning these associations.