Introduction: Although compliance with surveillance guidelines is crucial to epidemic diseases control, determinants of use of these guidelines in Nigeria are poorly documented. We assess health workers compliance and factors associated with the surveillance and response guidelines for epidemic-prone diseases in South-West Nigeria. Methods: In a cross-sectional study, 199 disease surveillance and notification officers in Oyo state were interviewed using a questionnaire on knowledge of disease surveillance and performance of surveillance activities. Data were analysed using descriptive statistics, chi-square and multiple logistic regression at P= 0.05. Results: Most surveillance units submitted disease outbreaks reports (81.48% at the health facility and 100% at the local government level). Timeliness and completeness of weekly reporting were 94% and 95% respectively. a quarter (25.9%) adhered to national case definitions guidelines. About 85.7% did laboratory case confirmation while 2.6% did facility level data analysis. Predictors for six months reporting activity include attending a training on surveillance and reporting (OR=7.92; CI=1.65–37.92), fund adequacy (OR=27.81; CI=7.68–100.60) and knowledge of surveillance dataflow (OR=4.80; CI=1.64–14.10). Conclusion: In addition to provision of adequate financial and laboratory resources, surveillance activities would benefit from continuous training on surveillance data flow.