What spiritual and psychological risks and benefits do people associate with psychedelics? We aimed to address these questions in a multimethod study. As part of a larger project, we did an internet survey of U.S. adults (N = 788; 41% reported prior psychedelic use) with both preregistered hypotheses and exploratory analyses, using Likert and open-ended items. Participants saw psychedelics carrying more psychological and practical risks (e.g., bad "trips," accidents, impaired judgment, legal problems) than psychospiritual benefits, which were endorsed more than spiritual struggles or risks. Highly endorsed psychospiritual benefits included awe, a deep sense of connection, and increased belief in a nonmaterial world. Other benefits included a greater sense of life meaning, profound spiritual experiences, new insights about ultimate reality, and deepened religious or spiritual beliefs. Participants rated interpersonal, moral, and doubt struggles higher than ultimate-meaning struggles, which were endorsed more than divine or demonic struggles. Perceived spiritual risks related positively to religiousness, Christian identification, religious community disapproval of psychedelics, and seeing the potential for demonic messages. Perceived benefits related positively to identifying as spiritual but not religious, past psychedelic use (especially positive or spiritual experiences), supernatural beliefs and experiences, religious community approval of psychedelics, and seeing psychedelics as doorways to positive spiritual messages. Qualitative analyses identified additional perceived risks (e.g., violence, death, reality confusion; financial and social problems; self-harm) and benefits (e.g., physiological and relational benefits; entertainment). These findings suggest that U.S. adults associate psychedelic use with a wide array of potential risks and benefits, including spiritual ones.