Purpose National culture has been shown to play a role in curriculum change in medical schools, and business literature has described a similar influence of organizational culture on change processes in organizations. This study investigated the impact of both national and organizational culture on successful curriculum change in medical schools internationally. Method The authors tested a literature-based conceptual model using multilevel structural equation modeling. For the operationalization of national and organizational culture, the authors used Hofstede's dimensions of culture and Quinn and Spreitzer's competing values framework, respectively. To operationalize successful curriculum change, the authors used two derivates: medical schools' organizational readiness for curriculum change developed by Jippes and colleagues, and change-related behavior developed by Herscovitch and Meyer. The authors administered a questionnaire in 2012 measuring the described operationalizations to medical schools in the process of changing their curriculum. Results Nine hundred ninety-one of 1,073 invited staff members from 131 of 345 medical schools in 56 of 80 countries completed the questionnaire. An initial poor fit of the model improved to a reasonable fit by two suggested modifications which seemed theoretically plausible. In sum, characteristics of national culture and organizational culture, such as a certain level of risk taking, flexible policies and procedures, and strong leadership, affected successful curriculum change. Conclusions National and organizational culture influence readiness for change in medical schools. Therefore, medical schools considering curriculum reform should anticipate the potential impact of national and organizational culture.