IntroductionTrend analyses of non-polio AFP and stool adequacy rates in Amhara Region showed optimal performance over the years. However, sub regional gaps continue to persist in certain zones where the reasons for low performance were not well documented. The objective of this study was to assess the performance of the disease surveillance and immunization system in Amhara Region, Ethiopia with emphasis on low performing woredas and zones.MethodsA descriptive cross-sectional study was conducted from July 2-10, 2015 to assess the structure, core and support surveillance functions in five zones and two town administrations that were purposively sampled based on differing performances, geographic location, and history of vaccine preventable disease outbreaks among others.ResultsOf the 82 sites reviewed, 71 (87%) have a designated surveillance focal person. Less than half 36(44%) of these focal persons have written terms of reference. Twenty-six (93%) of the health offices had a written surveillance work plan for the fiscal year. Only 17 (81%) of woreda health offices and town administrations had prioritized active surveillance sites into high, medium and low during the last 12 months. Only 4(17%) had independent active case search visits to these sites as per the priority. Seventy-eight (95%) and seventy-seven (94%) sites have a designated immunization focal person and updated EPI performance monitoring charts, respectively. There had been vaccine stock out in the 3 months before assessment in 28 (34%) of the sites.ConclusionThough there is an existence of well-organized surveillance network with adoption of the integrated disease surveillance and response, gaps exist in following the standard guidelines and operation procedures. Improvements needed in reporting site priority setting and regular visiting for active case search, outbreak investigation and management, vaccine supply and overall documentations.