Eighty-one subjects who used ayahuasca at least once in North America answered a lengthy set of open-ended questions and completed the 81-item After the Spiritual Experience Questionnaire. An additional 50 ayahuasca users were interviewed in person. The data for this study represent ayahuasca experience based on more than 2,267 ceremonies. A comparison group of 46 people attending a Catholic spiritual retreat weekend also completed the After the Spiritual Experience Questionnaire. A factor analysis of this questionnaire yielded three factors: Joy in Life, Relationship to the Sacred and Toxic Feelings. Although the ayahuasca users had significantly higher scores on the first two factors, the two groups had modest mean differences indicating a similar response to two very different spiritual experiences. This key finding strongly supports the view that ayahuasca users are engaged in an authentic process as spiritual in nature as that of the retreatants. The qualitative data revealed that ayahuasca users reduced their alcohol intake, ate healthier diets, enjoyed improved mood and greater self-acceptance and felt more loving and compassionate in their relationships. Seventy-four percent of the ayahuasca users said they had a relationship with and received ongoing guidance and support from the spirit of ayahuasca.