Accurate diagnosis in the Emergency Department (ED) is critical for appropriate, timely treatment. Discrepancies between admission diagnosis by the ED team and discharge diagnosis by the admission team may lead to suboptimal care and have important implications on patient outcomes, resource utilization and hospital quality measures. This study aimed to explore the extent of such discrepancies in a tertiary center in Saudi Arabia and their impact on patient outcomes. This retrospective study at a tertiary medical center in Riyadh, Saudi Arabia (July–August 2019), using electronic medical record (EMR) review, included patients aged ≥14 years old admitted through the adult emergency department. Patients admitted to the intensive care unit (ICU) or cardiac care unit (CCU), or triaged to the obstetrics and gynaecology (OBGYN) or psychiatric areas of the emergency department were excluded from the study. ED and discharge diagnoses were checked by three physicians and classified into three categories: full, partial and mismatch. A partial match was defined when the ED diagnosis correlated with the final diagnosis to a certain extent and the final diagnosis could not be revealed in the ED setting. Of 771 patients, 692 (89.8%) had matched initial and final diagnoses, 52 (6.7%) had a partially matched diagnosis, and 27 (3.5%) had a complete mismatch between their ED diagnosis and discharge diagnosis. Among partial matches (n = 52), the most frequently observed reason was Magentic Resonance Imaging (MRI) performed during admission (48.08%) and endoscopy/colonoscopy (15.39%). Duration of hospital stay was not significantly associated with diagnosis mismatch. Although the discrepancy between admission and discharge diagnoses was relatively low, careful evaluation of patient complaints, medical history and laboratory and imaging results is critical for accurate diagnosis and management. Future research is needed to explore the impact of discrepancies in diagnosis on patient outcomes and to identify strategies to minimize them.