Background: Reusing routinely recorded data from electronic hospital records (EHR) may offer a less-time consuming, and more real time alternative for monitoring compliance by nurses with a protocol for the safe preparation and administration of injectable medication. However, at present it is unknown if the data necessary to calculate the quality indicators (QIs) are recorded in EHRs, or if these data are suitable for automated QI calculation. Therefore, the aim of this study was to determine the feasibility of monitoring compliance by nurses with a protocol for the safe injectable medication preparation and administration by reusing routinely recorded EHR data for the automated calculation of QIs. Methods: A cross-sectional study in 12 Dutch hospitals (October 2015–May 2016). The checks included in the currently prevailing national protocol for the safe preparation and administration of injectable medication were translated into 16 data elements required to calculate the QIs. At each hospital, one interview was conducted using a structured questionnaire to decide whether the data elements were available in EHRs. To present these results, descriptive statistics were used. Results: In total, 20 health-care professionals were interviewed and four different EHR systems were evaluated. The availability of data elements was comparable between the four evaluated EHR systems. Nine of the 16 required data elements were recorded in EHRs, eight in a structured format. The seven missing data elements were mainly related to checks such as ‘gather all materials needed’ or ‘conduct hand hygiene’. Furthermore, changes were identified in the process for the preparation and administration of injectable medication. These changes are mostly related to the increased use of electronic medication administration registration and barcode medication administration systems. Conclusions: Reusing EHR data to monitor compliance by nurses with the currently prevailing protocol for the safe preparation and administration of injectable medication is not entirely feasible. A decision should be made on which checks should be recorded in the EHRs and which checks should be audited in order to minimize the registration burden for nurses. Moreover, the currently prevailing protocol should be revised to bring it in line with work-as-done. Our results can be used as guidance for such a revision and also for designing new QIs that can be calculated by reusing routinely recorded EHR data.