Background When placing orders into the electronic health record (EHR), prescribers often use free-text information to complement the order. However, the use of these free-text fields can result in patient safety issues. The objective of our study was to develop a deeper understanding of the conditions under which free-text information, or special instructions, are used in the EHR and the patient safety issues associated with their use, through an analysis of patient safety event (PSE) reports. Methods We identified 847 PSE reports submitted to the Pennsylvania Patient Safety Reporting System (PA-PSRS) between January 1, 2021, and December 31, 2022; this dataset was reduced to 677 after controlling for oversampling from particular facilities. After limiting to reports that mentioned the terms “special instructions,” “order instructions,” “order comments,” or “special comments,” we analyzed a total of 329 reports. A physician and human factors expert independently reviewed the reports and assigned each a code from the following categories: general care process, medication class, information expressed in the special instruction, special instruction issue, department or staff for which special instruction was intended, and whether the error reached the patient. Results Almost three quarters of the special instruction reports were related to Medication (n=233 of 329, 70.8%), followed by Laboratory/Blood Bank (n=54, 16.4%), and Radiology (n=23, 7.0%). Medication classes most frequently associated with special instructions included infectious disease medications (n=51 of 230, 22.2%), antithrombotic/antithrombotic reversal agents (n=32, 13.9%), and nutritional/electrolytes/intravenous fluids (n=32, 13.9%). Nearly one quarter each of medication-related special instructions were about timing (n=58 of 233, 24.9%) and dosing (n=54, 23.2%); most about laboratory/blood bank were related to the site of the blood draw (n=33 of 54, 61.1%), and many involving radiology were related to radiology/echocardiography instructions (n=16 of 23, 69.6%). The most frequent issues associated with special instructions were containing information contradictory to the order or other information (n=62 of 329, 18.8%); being confusing, incorrect, or used incorrectly (n=58, 17.6%); and not seen (n=25, 7.6%), not viewable (n=11, 3.3%), or instructions absent (n=11, 3.3%). In more than half of the reports, special instructions were intended for nursing staff (n=184 of 329, 55.9%), followed by pharmacy (n=49, 14.9%), radiology (n=21, 6.4%), and laboratory/blood bank (n=20, 6.1%). The error reached the patient in roughly three quarters (n=243 of 329, 73.9%) of the reports reviewed. Conclusion Special instructions are frequently used to provide additional context about medication orders and laboratory and radiology procedures and are often intended for nurses and pharmacists. However, these instructions can result in errors and may cause patient harm. Based on our analysis, we provide EHR design strategies and policies and protocols to address patient safety issues associated with free text to enable safer and more resilient care delivery.