The incidence of RCVS is unknown, but it is believed to be "not uncommon", and likely under-diagnosed. One small, possibly biased study found that the condition was eventually diagnosed in 45% of outpatients with sudden headache, and 46% of outpatients with thunderclap headache.

The average age of onset is 42, but RCVS has been observed in patients aged from 19 months to 70 years. Children are rarely affected. It is more common in females, with a female-to-male ratio of 2.4:1.

The direct cause of the symptoms is believed to be either constriction or dilation of blood vessels in the brain. The pathogenesis is not known definitively, and the condition is likely to result from multiple different disease processes.

Up to two-thirds of RCVS cases are associated with an underlying condition or exposure, particularly vasoactive or recreational drug use, complications of pregnancy (eclampsia and pre-eclampsia), and the adjustment period following childbirth called "puerperium". Vasoactive drug use is found in about 50% of cases. Implicated drugs include selective serotonin reuptake inhibitors, weight-loss pills such as Hydroxycut, alpha-sympathomimetic decongestants, acute migraine medications, pseudoephedrine, epinephrine, cocaine, and cannabis, among many others. It sometimes follows blood transfusions, certain surgical procedures, swimming, bathing, high altitude experiences, sexual activity, exercise, or coughing. Symptoms can take days or a few months to manifest after a trigger.

Following a study and publication in 2007, it is also thought SSRIs, uncontrolled hypertension, endocrine abnormality, and neurosurgical trauma are indicated to potentially cause vasospasm.