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Abstract Background Insulins, opioids, and antithrombotics are classified as high-alert medications (HAMs), posing a significant risk of serious patient harm when used in error. This study aimed to describe the frequency and nature of reported medication safety incidents involving these medicines in a Finnish university hospital. Methods This retrospective study analysed safety incidents involving insulins, antithrombotics, and opioids reported at Tampere University Hospital between January 2019 and December 2021. Quantitative methods, including content analysis, were used. Data were obtained from HaiPro, a web-based, voluntary incident reporting system used in Finnish healthcare, with reports submitted by healthcare professionals. Contributing factors related to the medication process were identified through quantitative content analysis of the incident reports. Results A total of 1,087 medication safety incidents involving insulins, opioids, and antithrombotic medications were reported during the study period, of which 983 were processed and included in the analysis. Of these, 79% involved patients, while 21% were classified as near miss. The most frequent types of incidents were related to medication administration (63%) and prescribing (22%). Antithrombotics accounted for 47% of the incidents, opioids for 35%, and insulins for 18%. The most common contributing factor for administration errors was failure to verify the medication order from the electronic medication list in the patient information system (20%). For prescribing errors, the most frequent contributing factors were entering the medication order in the wrong section or duplicating it in the patient information system. Conclusions This study identified the most common medication safety incidents and their contributing factors in the use of insulins, opioids, and antithrombotics. Errors most frequently occurred during administration and prescribing. These risks may be mitigated by developing and implementing safer practices throughout the medication process. The findings are relevant both nationally and internationally, as these high-alert medications are widely used across healthcare settings.