Background: Due to a dramatic increase in the past 20 years, the non-medical use of prescription drugs (NMUPD) has become a global public health issue. College students have high prevalence of NMUPD in the United States. However, limited studies have been conducted among Chinese students. The purposes of this study were to examine the prevalence of NMUPD among college students in two urban centers (Beijing and Macau) in China and assess its relationships with cultural orientation (collectivism - primary focus on the group and individualism - primary focus on the individual).