Application of an integrated Hospital Information System in Areteion University Hospital was launched 3 years ago. As it was the very first time that a fully fledged Hospital Information System was applied in complex university hospital environment, numerous problems and issues were brought up during this first period. The most critical issues are described in this paper, giving simply the essence of the problem and the general strategic line which was followed. Issues of hospital’s strategic goals, behavioural aspects of the users, technical problems of the software application, as well as issues of maturity of key players and tools per se and in their interaction, were faced by the management team of Hospital Information System.