We examined the relationship between use of progestagen-only before menopause (except for mini-pills) after the age of 40 and invasive breast cancer risk in 73 664 women from the French E3N cohort study (mean age at start of follow-up, 51.8 years; mean duration of follow-up, 9.1 years). A total of 2390 cases of invasive breast cancer were diagnosed during follow-up. Risk estimates were calculated using the Cox proportional hazard model. Overall, ever use of progestagen before menopause was not significantly associated with risk (relative risk (RR): 1.01, 95% confidence interval: 0.93-1.11). However, we observed a significant increase in risk associated with the duration of use (P-value for trend: 0.012), current use of progestagens for longer than 4.5 years being significantly associated with risk (RR: 1.44, 95% confidence interval: 1.03-2.00). Prolonged use of progestagens after the age of 40 may be associated with an increased risk of breast cancer and the subject needs to be investigated further.