Clomifene, also known as clomiphene, is a medication used to treat infertility in women who do not ovulate, including those with polycystic ovary syndrome. It is taken by mouth.

Common side effects include pelvic pain and hot flashes. Other side effects can include changes in vision, vomiting, trouble sleeping, ovarian cancer, and seizures. It is not recommended in people with liver disease or abnormal vaginal bleeding of unknown cause or who are pregnant. Clomifene is in the selective estrogen receptor modulator (SERM) family of medication and is a nonsteroidal medication. It works by causing the release of GnRH by the hypothalamus, and subsequently gonadotropin from the anterior pituitary.

Clomifene was approved for medical use in the United States in 1967. It is on the World Health Organization's List of Essential Medicines. Its introduction began the era of assisted reproductive technology.

Clomifene (particularly the purified enclomiphene isomer) has also been found to have a powerful ability to boost or restore testosterone levels in hypogonadal men. It can be used to enhance performance in sports and is banned by the World Anti-Doping Agency.

Clomifene is one of several alternatives for inducing ovulation in those who are infertile due to anovulation or oligoovulation. Evidence is lacking for the use of clomifene in those who are infertile without a known reason. In such cases, studies have observed a clinical pregnancy rate 5.6% per cycle with clomifene treatment vs. 1.3%–4.2% per cycle without treatment. Clomifene has also been used with other assisted reproductive technology to increase success rates of these other modalities.

Clomifene has been effectively used to restore spermatogenesis in trans women looking to have biological children. The effect of feminizing hormone therapy on fertility is not clear, but it is known that it can prevent sperm production.

Clomifene is sometimes used in the treatment of male hypogonadism as an alternative to testosterone replacement therapy.^{[non-primary source needed]} It has been found to increase testosterone levels by 2–2.5 times in hypogonadal men at such dosages. Despite the use of questionnaires in testosterone replacement comparator trials being called into question, clomifene's lower cost, therapeutic benefits, and greater value towards hypogonadism improvement have been noted.^{[non-primary source needed]}

Clomifene consists of two stereoisomers in equal proportion: enclomifene and zuclomifene. Zuclomifene has pro-estrogenic properties, whereas enclomifene is pro-androgenic, i.e. it promotes testosterone production through stimulation of the HPG axis. For this reason, purified enclomifene isomer has been found to be twice as effective in boosting testosterone compared to the standard mix of both isomers. Additionally, enclomifene has a half-life of just ten hours, but zuclomifene has a half-life on the order of several days to a week, so if the goal is to boost testosterone, taking regular clomifene may produce far longer-lasting pro-estrogenic effects than pro-androgenic effects.