BACKGROUND: Early detection and prompt reporting of epidemic prone diseases (EPD’s) has been cited as the pivot in the surveillance and control of outbreaks. The contributions by clinical staff towards early detections is highly relevant, however the level of knowledge and attitude towards reporting remains unknown. The study was therefore conducted to examine the knowledge and reporting standards of clinical staff towards outbreak investigations. METHODS: A cross sectional study design was conducted in Komfo Anokye Teaching Hospital (KATH), tertiary hospital in Kumasi-Ghana between February and May 2013. Stratified, simple random sampling was used to select 111 participants and a structured questionnaire used as the instrument for data collection. RESULTS: The mean age was 31.1(±6.8) years. About 87% (n=95/111) indicated knowledge of EPD’s. More than half of these, 62.1% (n=59/95) had no idea of the definition and 30.5% (n=29/95) gave correct definition of EPD’s but had limited knowledge on the laboratory specimen required for its investigation. About 48% (n=46/95) of the respondents indicated that they would consult the nurse-in-charge of the ward instead of the public health official when an outbreak is suspected. CONCLUSION: The knowledge level of EPD’s was generally low but was found to be high with meningitis and poliomyelitis. The study has shown that the procedure for reporting EPD’s remains a challenge in the Komfo Anokye Teaching Hospital. A protocol on outbreak investigation procedures would address the gaps identified in the study.