Secular trends in diagnostic code density in electronic healthcare data from health care systems in the Vaccine Safety Datalink Project

► We assessed the secular trends in diagnostic code density during 2001-2009. ► An increasing trend in diagnostic code density was observed across all sites. ► Sudden changes were observed when changes in coding policies or data inclusion criteria took place. ► Inappropriate historical comparator may introduce a false positive association between a vaccine and an adverse event. ► Ongoing monitoring of the diagnostic code density may provide guidance on choice of study design and comparison groups.