OBJECTIVES: To estimate the prevalence of potential interactions between antiplatelet drugs, anticoagulants, digoxin and Chinese medications (CM) and further to explore the determining factors associated with the occurrence of potential interactions.  METHODS: This study assessed the prevalence of exposure to the major interactions between the seven selected western medications commonly used for the cardiovascular diseases (i.e., aspirin, clopidogrel, digoxin, dipyridamole, heparin, ticlopidine, and warfarin [in terms of high risk western medications, HRWM]) and selected common used CM (i.e., American ginseng, Asian ginseng, danshen, and dong quai), using the two-million National Health Insurance (NHI) Research Database in Taiwan. Both univariate and multivariate logistic regression analyses were conducted to identify the contributing factors (e.g., baseline demographics, comorbidities, health services utilizations) of potential major interactions incidence.  RESULTS: While 14.7% of HRWM users (19,431/131,804) ever used those selected CM concurrently at anytime in 2007, 81.9% (15,919/19,431) of HRWM-CM concurrent users had been exposed to at least one combination of potential major interactions. Anticoagulants (i.e., heparin and warfarin) users were more likely to be prescribed with the selected CM with major interactions (86.7% and 86%, respectively). The concomitant use of aspirin with dong quai or Asian ginseng was more prevalent than others. The factors that statistically significantly associated with the incremental exposure of potential major interactions included female sex, age 45-84 years old, higher number of outpatient visits, distinct medications prescribed, and previous diagnosis of stroke. In contrast, those HRWM-CM users with high monthly income, enrolled in the West region of Taiwan NHI, and had previous history of acute respiratory infection were less likely to exposure to the major interactions of HRWM-CM use.   CONCLUSIONS: The exposure of the major interactions with CM was relative prevalent among HRWM users in Taiwan. Further research is needed to investigate the outcomes associated with such combinations.