<p>Using structural equation modeling to analyze two waves of longitudinal data from 306 adults on the autism spectrum in the USA, we assessed whether transcendent spirituality (feeling connected to a higher being) was associated with psychological flexibility (the ability to respond to uncomfortable internal sensations in a flexible, values-driven manner), psychological inflexibility, and satisfaction with life over a 10-week period. While we identified no significant associations between transcendent spirituality and psychological inflexibility, we found that spirituality was longitudinally associated with psychological flexibility and satisfaction with life. Psychological flexibility mediated the association between spirituality and satisfaction with life. Implications are offered.</p>