Aims: A comparison of conventional instruments and instruments with needle protection technology (NPT) with respect to the incidence of needlestick injuries (NSI) and an assessment of the practicability of the instruments was performed at the university clinic in Heidelberg. Further goals were to validate the reporting rate of NSI in this clinic, to increase the awareness of NSI among the employees, to improve safety behaviour and finally, to come to a recommendation regarding the use of NPT. Methods: Three study groups each consisting of six comparable wards were established: group I was the control group (no intervention), groups II and III received special training in safety behaviour and group III also used instruments with NPT for a period of 12 months (intervention period). Results: The number of reported needlestick injuries decreased significantly in group III. The employees’ assessment of the practicability of the safety instruments showed an improvement during the investigation period too. Conclusions: A standardized reporting system for NSI is necessary to improve occupational safety within the health care sector. In 2004, at the end of the study, it became clear that further tests of the various instruments with NPT will be needed. The use of the instruments with NPT used in this study and authorized in Germany can be recommended for the reduction of NSI, provided that the disposal containers recommended by the TRBA (Technical Rules for Biological Agents) 250 are used.