This study investigated the major NIS implementation factors and their capability of predicting the effectiveness of NIS implementation by using the clinical information systems success model. The triangulation method was employed in this study. A total of 348 nurses were recruited from regional hospitals in two districts of Taipei through purposive sampling. Research data were collected through questionnaires and focus group interviews 3 and 6 months after an NIS was implemented at their hospital. The result show the explanatory power of use dependence, use satisfaction, and net benefits in predicting NIS effectiveness was approximately 64.5%-89.4%. The explanatory power of net benefits in predicting NIS effectiveness after 3 and 6 months exceeded 80%. The nurses reported that NIS implementation changed their workflow and positively influenced medication administration safety. This study empirically identified the critical factors that affect the successful implementation of NISs and reported the nurses' experience of NIS use.