Background: Experiences of having an encounter with seemingly autonomous entities are sometimes reported after inhaling N,N-dimethyltryptamine. Aim: The study characterized the subjective phenomena, interpretation, and persisting changes that people attribute to N,N-dimethyltryptamine-occasioned entity encounter experiences. Methods: Two thousand, five hundred and sixty-one individuals (mean age 32 years; 77% male) completed an online survey about their single most memorable entity encounter after taking N,N-dimethyltryptamine. Results: Respondents reported the primary senses involved in the encounter were visual and extrasensory (e.g. telepathic). The most common descriptive labels for the entity were being, guide, spirit, alien, and helper. Although 41% of respondents reported fear during the encounter, the most prominent emotions both in the respondent and attributed to the entity were love, kindness, and joy. Most respondents endorsed that the entity had the attributes of being conscious, intelligent, and benevolent, existed in some real but different dimension of reality, and continued to exist after the encounter. Respondents endorsed receiving a message (69%) or a prediction about the future (19%) from the experience. More than half of those who identified as atheist before the experience no longer identified as atheist afterwards. The experiences were rated as among the most meaningful, spiritual, and psychologically insightful lifetime experiences, with persisting positive changes in life satisfaction, purpose, and meaning attributed to the experiences. Conclusion: N,N-dimethyltryptamine-occasioned entity encounter experiences have many similarities to non-drug entity encounter experiences such as those described in religious, alien abduction, and near-death contexts. Aspects of the experience and its interpretation produced profound and enduring ontological changes in worldview.