Teachers' fidelity of implementation of substance use prevention curricula is widely considered desirable and is linked empirically to effectiveness. The authors examine factors pertinent to teachers' fidelity to curricula guides, using data from a nationally representative sample of 1,905 lead substance use prevention teachers in the nation's public and private schools. Findings suggest that about one-fifth of teachers of substance use prevention curricula did not use a curriculum guide at all, whereas only 15% reported they followed one very closely. Positively associated with adherence were teachers' discretion in their coverage of prevention lessons, beliefs concerning the effectiveness of the most recent training they received and the curricula they taught, and level of support they received from their principals for substance use prevention. The authors conclude that some degree of curriculum adaptation is inevitable and suggest how adherence to curricula guides may be improved through teacher training.