Hospital information system (HIS) implementation has become an important part of health informatics construction in China. However, effective use of HIS in the Chinese context has scarcely been discussed in the academic literature. Drawing upon Burton-Jones and Grange's (2013) effective use theory, this paper investigates the antecedents of medical workers’ effective use of HIS and the relationships between the antecedents in the Chinese context from a post-acceptance perspective. It employs a mixed-method approach in which a qualitative study was conducted to identify the antecedents and to develop the hypotheses, and a quantitative study was conducted to verify the hypotheses. The qualitative data (from in-depth interviews) and quantitative data (from a questionnaire survey) were collected from five public hospitals in north-eastern China. The meta-inferences from this study show that: (i) effective use of HIS is jointly determined by self-efficacy, management support, information quality and system quality; (ii) management support strengthens the effect of self-efficacy on effective use of HIS for female workers but not for male workers; and (iii) self-efficacy has a significant positive effect on female workers’ effective use of HIS but is not significant for male workers, while information quality has a significant positive effect on male workers’ effective use of HIS but is not significant for female workers. This paper extends effective use theory and enriches HIS research with practical implications for HIS implementation in China and other developing countries.