User acceptance is a precondition for successful implementation of hospital information systems (HISs). Increasing investment in information technology by healthcare organisations internationally has made user acceptance an important issue in technology implementation and management. Despite the increased focus on hospital information systems, there continues to be user resistance. The present study aimed to investigate the factors affecting hospital information systems nurse-user acceptance of HISs, based on the Unified Theory of Acceptance and Use of Technology (UTAUT), in the Shiraz University of Medical Sciences teaching hospitals. A descriptive-analytical research design was employed to study nurses' adoption and use of HISs. Data collection was undertaken using a cross-sectional survey of nurses (n=303). The research model was examined using the LISREL path confirmatory modeling. The results demonstrated that the nurses' behavioural intention (BI) to use hospital information systems was predicted by Performance Expectancy (PE) (β= 2.34, p<0.01), Effort Expectancy (EE) (β= 2.21, p<0.01), Social Influence (SI) (β= 2.63, p<0.01) and Facilitating Conditions (FC) (β= 2.84, p<0.01). The effects of these antecedents of BI explained 72.8% of the variance in nurses' intention to use hospital information systems (R2 = 0.728). Application of the research model suggested that nurses' acceptance of HISs was influenced by performance expectancy, effort expectancy, social influence and facilitating conditions, with performance expectancy having the strongest effect on user intention.