This article presents the results of a study conducted to prospectively assess the relationship between spirituality and number of alcoholic drinks among Chilean adolescents while controlling for extraneous factors. A convenience sample of 661 adolescent-parent pairs from Santiago, Chile, completed an interviewer-administered questionnaire between 2007 and 2010, when adolescents were 12 to 17 years old), and between 2008 and 2011, when they were 14 to 19 years old. Participants were asked about alcohol-using behaviors, behavioral problems, religious involvement, spirituality, parenting, and demographics. Propensity score stratification analysis using negative binomial regression identified a heterogeneous and inverse association between spirituality and number of alcoholic drinks consumed in the past 30 days (b = -0.770, p =.002). However, under the heterogeneity assumption, spirituality was significantly and inversely associated with the number of alcoholic drinks only for adolescents with the highest (b = -1.608, p =.015) and next-highest (b = 1.852, p =.012) propensity to be spiritual. The findings provide greater understanding of spirituality's potential and its limitations as a protective factor and can inform social work prevention efforts for at-risk youths and, more specifically, for youths who may be less responsive to the protective dimensions of spirituality.