A large body of historical evidence describes the use of hallucinogenic compounds, such as psilocybin mushrooms, for religious purposes. But few scientific studies have attempted to measure or characterize hallucinogen‐occasioned spiritual experiences. The present study examined the factor structure of the Mystical Experience Questionnaire (MEQ), a self‐report measure that has been used to assess the effects of hallucinogens in laboratory studies. Participants (N = 1,602) completed the 43‐item MEQ in reference to a mystical or profound experience they had had after ingesting psilocybin. Exploratory factor analysis of the MEQ retained 30 items and revealed a four‐factor structure covering the dimensions of classic mystical experience: unity, noetic quality, sacredness (F1); positive mood (F2); transcendence of time/space (F3); and ineffability (F4). MEQ factor scores showed good internal reliability and correlated with the Hood Mysticism Scale, indicating convergent validity. Participants who endorsed having had a mystical experience on psilocybin, compared to those who did not, had significantly higher factor scores, indicating construct validity. The four‐factor structure was confirmed in a second sample (N = 440) and demonstrated superior fit compared to alternative models. The results provide initial evidence of the validity, reliability, and factor structure of a 30‐item scale for measuring single, hallucinogen‐occasioned mystical experiences, which may be a useful tool in the scientific study of mysticism.