Background: A functioning disease surveillance and reporting system has been a serious challenge to developing countries; and as such, effective strategies to strengthen capacity for early disease out- break detection is required. The main objective was to determine knowledge, attitude, practice and challenges of disease reporting among health care workers and the comparison thereof across the geopolitical zones in a South Eastern State, Nigeria. Methods: A cross sectional descriptive design, used stratified simple random sampling technique to select health care workers from three geopolitical zones in a South Eastern State, Nigeria. Data was collected using a pretested semi structured questionnaire and an observational checklist. Descriptive analyses and statistical inferences were done with p set at 0.05 significant levels. Results: Majority of respondents indicated that they knew what disease reporting is (89.1%) but only two thirds (66.7%) were aware of disease reporting forms and of those aware, between 11and 24% did not know or correctly identify the uses of one type of form or the other. Majority were of the opinion that disease reporting was a cumbersome activity (67.3%) with inadequate supply of forms (52.4%). About 74% had not reported a disease before or received training in disease reporting. Furthermore, there were significant differences between the respondents from the different geopolitical zones with respect to knowledge, attitude and practice of disease reporting (p Conclusions: Health care workers are faced with multiple challenges. Therefore to ensure effective disease reporting; strategies that secure political commitments, adequate and equitable funding with regular training should be implemented.Key words: KAP, Disease reporting, Health workers, Imo, Nigeria