Objective: The effectiveness of federal prison-based residential drug and alcohol treatment programs was evaluated using event history procedures that addressed the problem of selection bias and included a wide range of control variables. Methods: The sample comprised 760 treatment subjects and 809 comparison subjects. Treatment subjects were from 20 different prisons of medium, low, and minimum security levels. Comparison subjects were drawn from over 30 prisons. Results: The results indicated that individuals who entered and completed in-prison residential treatment were less likely to experience the critical postrelease outcomes of new arrests and substance use during the first 6 months following release. Conclusions: Without controlling for selection bias, the effects of treatment would most likely have been attenuated. The results have greater generalizability than other studies of prison-based treatment. This study occurred within a multisite context of 20 programs serving both male and female inmates and operating within different security levels and different geographic regions.