To investigate the role of religiosity in the earliest stages of drug involvement, the authors studied recent-onset occurrence of first chances to try a drug and first actual drug use, expressed as a function of religious practice behaviors, levels of religious devotion, and religious affiliation. Based upon standardized questionnaire assessments of nationally representative samples of school-attending youths drawn in Panama, the five Spanish heritage countries of Central America, and the Dominican Republic (n = 12,797), the 1999-2000 study estimates indicate that higher levels of religious practice are inversely associated with the earliest stages of tobacco and cannabis experiences (i.e., the first chance to try and the first actual use) but not so for alcohol. To illustrate, for each unit increase in levels of religious practice behaviors, there was an associated reduced occurrence of the first chance to try tobacco (odds ratio = 0.76, 95% confidence interval: 0.62, 0.94). Occurrence of first actual use of tobacco and cannabis was not associated with levels of religious practice behaviors among youths exposed to the opportunity to try these drugs. As such, these behaviors apparently have not strengthened resistance. Rather, autarcesis may be at work, functioning to shield youths from drug exposure opportunities.