Background Effective therapies for reducing cardiovascular disease (CVD) risk in people with elevated lipoprotein(a) are lacking, especially for primary prevention. Because of the potential association of lipoprotein(a) with thrombosis, we evaluated the relationship between aspirin use and CVD events in people with elevated lipoprotein(a). Methods and Results We used data from the MESA (Multi‐Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of baseline cardiovascular disease. Due to potential confounding by indication, we matched aspirin users to nonusers using a propensity score based on CVD risk factors. We then evaluated the association between aspirin use and coronary heart disease (CHD) events (CHD death, nonfatal myocardial infarction) stratified by baseline lipoprotein(a) level (threshold of 50 mg/dL) using Cox proportional hazards models with adjustment for CVD risk factors. After propensity matching, the study cohort included 2183 participants, including 1234 (57%) with baseline aspirin use and 423 (19%) with lipoprotein(a) >50 mg/dL. Participants with lipoprotein(a) >50 mg/dL had a higher burden of CVD risk factors, more frequent aspirin use (61.7% versus 55.3%, P =0.02), and higher rate of incident CHD events (13.7% versus 8.9%, P <0.01). Aspirin was associated with a significant reduction in CHD events among those with elevated lipoprotein(a) (hazard ratio, 0.54 [95% CI, 0.32–0.94]; P =0.03). Those with lipoprotein(a) >50 mg/dL and aspirin use had similar CHD risk as those with lipoprotein(a) ≤50 mg/dL regardless of aspirin use. Conclusions Aspirin use was associated with a significantly lower risk for CHD events in participants with lipoprotein(a) >50 mg/dL without baseline CVD. The results of this observational propensity‐matched study require confirmation in studies with randomization of aspirin use.