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Oral contraceptives may influence coagulation, increasing the risk of deep venous thrombosis (DVT) and pulmonary embolism, stroke and myocardial infarction (heart attack). The Stroke Journal said that OCs confer "risk of first ischemic stroke."^[1] The Journal of Clinical Endocrinology & Metabolism also concluded in 2005 that "a rigorous meta-analysis of the literature suggests that current use of low-dose OCs significantly increases the risk of both cardiac and vascular arterial events."^[2]

Combined oral contraceptives are generally accepted to be contraindicated in women with pre-existing cardiovascular disease, in women who have a familial tendency to form blood clots (such as familial factor V Leiden), women with severe obesity and/or hypercholesterolemia (high cholesterol level), and in smokers over age 35.

Recent scientific research has shown that there is evidence that these pills are carcinogenic,^[3] at the same time they decrease the risk of ovarian cancer, endometrial cancer,^[4] and colorectal cancer.^[5] They confer a risk of first schemic stroke,^[1] and significantly increase the risk of cardio-vascular disease.^[2] These pills also lead to increased deep vein thrombosis.

The risk of thromboembolism varies with different preparations; With second-generation pills (with an estrogen content less than 50μg), the risk of thromboembolism is small with an incidence of approximately 15 per 100,000 users per year, compared with 5 per 100,000 users per year among non-pregnant individuals not taking the pill, and 60 per 100,000 pregnancies.^[6] In individuals using preparations containing third-generation progestogens (desogestrel or gestodene), the incidence of thromboembolism is approximately 25 per 100,000 users per year.^[6] Also, the risk is greatest in subgroups with additional factors, such as smoking (which increases risk substantially) and long-continued use of the pill, especially in women over 35 years of age.^[6]

Monograph 91 of The International Agency for Research on Cancer (IARC) stated in 2005 that "there is sufficient evidence in humans for the carcinogecity of combined estrogen-progestogen contraceptives."^[3][7] Research into the relationship between breast cancer risk and hormonal contraception is complex and seemingly contradictory.^[8] The large 1996 collaborative reanalysis of individual data on over 150,000 women in 54 studies of breast cancer found that: "The results provide strong evidence for two main conclusions. First, while women are taking combined oral contraceptives and in the 10 years after stopping there is a small increase in the relative risk of having breast cancer diagnosed. Second, there is no significant excess risk of having breast cancer diagnosed 10 or more years after stopping use. The cancers diagnosed in women who had used combined oral contraceptives were less advanced clinically than those diagnosed in women who had never used these contraceptives."^[9] This data has been interpreted to suggest that oral contraceptives have little or no biological effect on breast cancer development, but that women who seek gynecologic care to obtain contraceptives have more early breast cancers detected through screening.^[10][11] While taking the pill, there are approximately 0.5 excess cancers per 10,000 women aged 16–19, and approximately 5 excess cancers per 10000 women aged 25–29.^[6]

Crooks and Baur said that the health risks of oral contraceptives are lower than those from pregnancy and birth,^[12] and "the health benefits of any method of contraception are far greater than any risks from the method".^[13] Some organizations have argued that comparing a contraceptive method to no method (pregnancy) is not relevant—instead, the comparison of safety should be among available methods of contraception.^[14]