This paper presents the results of a study to determine factors influencing perceptions and attitudes of nurses towards the use of ICT in 16 hospitals in KwaZulu-Natal (KZN) province, South Africa. Data were collected through a survey questionnaire and factor analysis performed to extract relevant variables. Overall, results revealed positive dispositions of nurses towards the use of ICT. Results further revealed self-efficacy, adoption of computers to improve nursing care, confidence in using computers; usefulness; interactability and knowledgeability were major factors influencing perceptions and attitudes of nurses towards use of ICT at the work place. Findings may inform institutional and provincial ICT infrastructure development decisions to improve nursing services in hospitals. Theoretically the study provides an understanding of factors influencing attitudes and perceptions of nurses’ in the use of ICT at work place from a developing country context such as South Africa and also in vast rural province such as KZN.