Preparing participants for psychedelic experiences is crucial for ensuring these experiences are safe, and potentially, beneficial. However, there is currently no validated measure to assess the extent to which participants are well-prepared for such experiences. Our study aimed to address this gap by developing, validating, and testing the Psychedelic Preparedness Scale (PPS). Using a novel iterative Delphi-focus group methodology (‘DelFo’) followed by qualitative pre-test interviews, we incorporated the perspectives of expert clinicians/researchers and of psychedelic users, to generate items for the scale. Psychometric validation of the PPS was carried out in two large online samples of psychedelic users (N = 516; N = 716), and the scale was also administered to a group of participants before and after a 5–7-day psilocybin retreat (N = 46). Exploratory and confirmatory factor analysis identified four factors from the 20-item PPS: Knowledge-Expectations, Intention-Preparation, Psychophysical-Readiness, and Support-Planning. The PPS demonstrated excellent reliability (ω = 0.954) and evidence supporting convergent, divergent and discriminant validity was also obtained. Significant differences between those scoring high and low (on psychedelic preparedness) before the psychedelic experience were found on measures of mental health/wellbeing outcomes assessed after the experience, suggesting that the scale has predictive utility. By prospectively measuring modifiable pre-treatment preparatory behaviours and attitudes using the PPS, it may be possible to determine whether a participant has generated the appropriate mental ‘set’ and is therefore likely to benefit from a psychedelic experience, or at least, less likely to be harmed.