The use of estrogen, either alone or, more commonly, in combination with a progestin, is common throughout a woman’s life, but it is associated with an increased risk of venous thromboembolism (VTE). This serious adverse effect depends on the administration regimen (type and dose of estrogen, route of administration, type of progestin) and the clinical context. Combined oral contraceptives (COCs) are the most commonly used hormonal forms, and all increase the risk of VTE. This increase is minimal with COCs containing low doses of ethinylestradiol and levonorgestrel. Newer generations of COCs are generally the most thrombogenic. The excess risk of VTE associated with menopausal hormone therapy is more pronounced due to the women’s advanced age. It can be reduced by using transdermal estrogens alone or in combination with progesterone. The differential effect of estradiol on blood coagulation depending on its route of administration is demonstrated in randomized mechanistic studies. The risk of VTE is considerably increased in high-risk women (obesity, history of VTE, genetic risk factors for VTE) using oral estrogens. A substantial proportion of adverse events could be prevented by adhering to current recommendations. Improving the safety of estrogen use involves, in particular, better individual risk stratification and a personalized approach.