Abstract Background: Epidemiologic evidence is insufficient to draw conclusions on the impact of low-dose aspirin use on breast cancer risk, and the potential impact of other antiplatelet drugs such as clopidogrel needs to be explored. Methods: We investigated the association between breast cancer risk and low-dose aspirin or clopidogrel use in the E3N cohort, which includes 98,995 women, with information on breast cancer risk factors collected from biennial questionnaires matched with drug reimbursement data available from 2004. Women with at least two reimbursements of the drug of interest in any previous 3-month period were considered “ever” exposed. Exposure was considered as time-varying and multivariable Cox regression models were used to estimate HRs of breast cancer. Results: Among 62,512 postmenopausal women followed during 9 years on average, 2,864 breast cancer cases were identified. Compared with never use, a transient higher breast cancer risk was observed during the third year of low-dose aspirin use [HR2–≤3 years of use = 1.49 (1.08–2.07)], followed by a lower risk [HR4+ years of use = 0.72 (0.52–0.99)]. Clopidogrel ever use was associated with a higher breast cancer risk [HR, 1.30 (1.02–1.68)], restricted to estrogen receptor negative (ER−) tumors [HRER+ = 1.14 (0.83–1.57), HRER− = 3.07 (1.64–5.76), Phomogeneity = 0.01]. Conclusions: Low-dose aspirin was associated with a lower breast cancer risk only after several years of use, while ever use of clopidogrel was associated with a higher ER− breast cancer risk. Impact: Antiplatelet drugs are not good pharmacologic candidates for breast cancer prevention.