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Objectives: The Chinese government has greatly increased funding for disease control and prevention since the 2003 Severe Acute Respiration Syndrome crisis, but it is also concerned whether these increased resources have been used efficiently to improve public health services. We aimed to assess the efficiency of county-level Centers for Disease Control and Prevention (CDCs) of China and to identify strategies for optimising their performance., Methods: A total of 446 county-level CDCs were selected based on systematic sampling throughout China. The data envelopment analysis framework was used to calculate the efficiency score of sampled CDCs in 2010. The Charnes, Cooper and Rhodes (CCR) model was applied to calculate the overall and scale efficiency, and the Banker, Charnes and Cooper (BCC) model was used to assess technical efficiency. Models included three inputs and seven outputs. A projection analysis was conducted to identify the difference between projection value and actual value for inputs and outputs., Results: The average overall efficiency score of CDCs was 0.317, and the average technical efficiency score was 0.442 and 88.3% with decreasing returns to scale. Projection analysis indicated that all seven categories of outputs were underproduced. CDCs in the eastern region tended to perform better than CDCs in the middle and the western region., Conclusions: Most county-level CDCs in China were operated inefficiently. Emphasis should be put on increasing staff and general operating expenses through current governmental funding, upgrading healthcare providers' competencies and enhancing the standardisation of operational management, so that CDCs could utilise their resources more efficiently., (© 2016 John Wiley & Sons Ltd.)