Abstract Background The purpose of patient safety is to prevent harm occurring in the healthcare system. Patient safety is improved by the use of a reporting system in which healthcare workers can document and learn from incidents, and thus prevent potential medical errors. The present study aimed to determine patient safety challenges facing clinicians (physicians and nurses) in emergency medicine and to assess barriers to using e-OVR (electronic occurrence variance reporting). Methods This cross-sectional study involved physicians and nurses in the emergency department (ED) at King Khalid University Hospital (KKUH) in Riyadh, Saudi Arabia. Using convenience sampling, a self-administered questionnaire was distributed to 294 clinicians working in the ED. The questionnaire consisted of items pertaining to patient safety and e-OVR usability. Data were analyzed using frequencies, means, and percentages, and the chi-square test was used for comparison. Results A total of 197 participants completed the questionnaire (67% response rate) of which 48 were physicians (24%) and 149 nurses (76%). Only 39% of participants thought that there was enough staff to handle work in the ED. Roughly half (48%) of participants spoke up when something negatively affected patient safety, and 61% admitted that they sometimes missed important patient care information during shift changes. Two-thirds (66%) of the participants reported experiencing violence. Regarding e-OVR, 31% of participants found reporting to be time consuming. Most (85%) participants agreed that e-OVR training regarding knowledge and skills was sufficient. Physicians reported lower knowledge levels regarding how to access (46%) and how to use (44%) e-OVR compared to nurses (98 and 95%, respectively; p < 0.01). Less than a quarter of the staff did not receive timely feedback after reporting. Regarding overall satisfaction with e-OVR, only 25% of physicians were generally satisfied compared to nearly half (52%) of nurses. Conclusion Although patient safety is well emphasized in clinical practice, especially in the ED, many factors hinder patient safety. More awareness is needed to eliminate violence and to emphasize the needs of additional staff in the ED. Electronic reporting and documentation of incidents should be well supported by continuous staff training, help, and feedback.