Background: Since the beginning of 2007, the National Health Research Institutes has provided evidence-base medicine (EBM) information resource support, including free access to the Cochrane Library, and promotional activities in the regional teaching hospitals of Taiwan. Objectives: This study aims to identify the relationship between physicians’ self-efficacy in EBM improvement with their perception, barriers and behavior toward EBM. Methods: A cross-sectional postal questionnaire was sent to the physicians of 14 regional teaching hospitals that were randomly selected by cluster sampling during October 2008 to February 2009. All physicians in the selected hospitals participated in this survey. The physicians who had a significant improvement in their attitude, belief and behavior of EBM within one year were enrolled into the favorable group (n = 251). In contrast, subjects who did not perceive significant improvement regarding EBM were categorized as the unfavorable group (n = 293). Results: The physicians in the favorable group were more likely to use the electronic resources (p & 0.001) and online database (p & 0.05) to retrieve EBM information, especially on English online database (p & 0.05). The multivariate liner regression analysis also indicated that they had more favorable perceptions (β = 0.387, p & 0.001) including current attitude, perceived knowledge or skill and understanding of technical term. The barriers of applying EBM they encountered were lower (β = −0.132, p & 0.01) than the unfavorable group. They were more often accessing the online evidence retrieval systems to search medical information (β = 0.031, p & 0.05). Conclusions: The perceived improvement in adopting EBM could play an important role for physicians to apply EBM. Our study suggests that raising the physicians’ self-efficacy in EBM improvement will accelerate and enhance the implementation of EBM.