Introduction: When serious medication errors (ME) are identified, communication to the field may be necessary. In the EU, communication of serious safety issues, such as medication errors associated with adverse drug reactions, is done through direct healthcare professional communications (DHPCs). We aimed to identify how often DHPCs about medication errors are distributed, and we explored factors associated with these ME DHPCs. Methods: We performed a descriptive study of all centrally authorised products (CAPs) approved before 1 May 2019 in the EU. All DHPCs issued between 1 January 2001 and 1 May 2019 were reviewed for ME content. Characteristics of CAPs were collected from the website of the European Medicines Agency. A Kaplan–Meier survival analysis was performed to estimate the 5- and 10-year probability of the occurrence of a first ME DHPC. A logistic regression was performed to explore risk factors for ME DHPCs. Results: A total of 678 CAPs were included, of which 35 required an ME DHPC during the study period. The 5-year probability for a CAP to have a first ME DHPC was 2.5% (95% CI 1.1–3.9) and the 10-year probability was 4.4% (95% CI 2.2–6.5). Among products with an ME DHPC, the 5-year probability of a second ME DHPC was 21.3% (95% CI 0.2–38.0). The risk of ME DHPCs was increased for products with multiple pharmaceutical formulations, enteral liquid or parenteral injection preparations, and products classified as nervous system agents or antineoplastic and immunomodulating agents. Conclusions: The absolute number of ME DHPCs for CAPs is low and does not give rise to immediate concern. We identified potential risk factors for ME DHPCs that should be taken into account during approval procedures or line extensions.