Background: The effectiveness of school-based tobacco use prevention programs depends on proper implementation. This study examined factors associated with teachers' implementation of a smoking prevention curriculum in a cluster randomized trial called Project SPLASH (Smoking Prevention Launch Among Students in Hawaii). Methods: A process evaluation was conducted and a cross-condition comparison used to examine whether teacher characteristics, teacher training, external facilitators and barriers, teacher attitudes, and curriculum attributes were associated with the dose of teacher implementation in the intervention and control arms of the study. Data were collected from a total of 62 middle school teachers in 20 public schools in Hawaii, during the 2000-2001 and 2001-2002 school years. Sources included teacher questionnaires and interviews. Chi-square test and t test revealed that implementation dose was related to teachers' disciplinary backgrounds and skills and student enjoyment of the curriculum. Results: Content analysis, within case, and cross-case analyses of qualitative data revealed that implementing the curriculum in a yearlong class schedule and high teacher self-efficacy supported implementation, while high perceived curriculum complexity was associated with less complete implementation. Conclusions: The results have implications for research, school health promotion practice, and the implementation of evidence-based youth tobacco use prevention curricula. (Contains 4 tables and 2 figures.)