Background. Well-functioning surveillance systems are crucial for effective disease control programs. The Integrated Disease Surveillance and Response (IDSR) strategy was developed and adopted in 1998 for Africa as a comprehensive public health approach and subsequently, Ghana adopted the IDSR technical guidelines in 2002. Since 2012, the IDSR data is reported through the new District Health Information Management System II (DHIMS2) network. The objective was to evaluate the Integrated Disease Surveillance and Response (IDSR) system in northern Ghana. Methods. This was an observational study using mixed methods. Weekly and monthly IDSR data on selected infectious diseases were downloaded and analyzed for 2011, 2012 and 2013 (the years before, of and after DHIMS2 implementation) from the DHIMS2 databank for the Upper East Region (UER) and for two districts of UER. In addition, key informant interviews were conducted among local and regional health officers on the functioning of the IDSR. Results. Clinically diagnosed malaria was the most prevalent disease in UER, with an annual incidence rate close to 1. Around 500 suspected HIV/AIDS cases were reported each year. The highest incidence of cholera and meningitis was reported in 2012 (257 and 392 cases respectively). Three suspected cases of polio and one suspected case of guinea worm were reported in 2013. None of the polio and guinea worm cases and only a fraction of the reported cases of the other diseases were confirmed. A major observation was the large and inconclusive difference in reported cases when comparing weekly and monthly reports. This can be explained by the different reporting practice for the sub-systems. Other challenges were low priority for surveillance, ill-equipped laboratories, rare supervision and missing feedback. Conclusions. The DHIMS2 has improved the availability of IDSR reports, but the quality of data reported is not sufficient. Particularly the inconsistencies between weekly and monthly data need to be addressed. Moreover, support for and communication within the IDSR system is inadequate and calls for attention.