Objectives The aim of the present study was to examine some initial results and learning curves concerning subxiphoid single-port thymectomy (SSPT), thereby clarifying the safety of this surgical approach and describing the precautions for adopting it. Methods From March 2011 to August 2019, a total of 203 patients underwent thymectomy for either anterior mediastinal tumours or myasthenia gravis at Fujita Health University Hospital. Of these 203 patients, 147 patients who had undergone SSPT were selected as participants for the present study. Results Of the 147 cases, transition to a different approach was required in three (2.0%) cases: two (1.3%) cases transitioned to median sternotomy, whereas one (0.7%) case transitioned to the side chest trans-intercostal approach. The two cases that transitioned to median sternotomy were the second cases for different operators after they began performing this technique. There were six (4.0%) cases with complications and no deaths. The operation time cumulative summation learning curve analysis revealed that the curves descended from the 38th case. In the 83 cases handled by one surgeon, the learning curves descended from the 31st case. Conclusions SSPT is a safe modality with few complications and no associated cases of mortality reported. Operators are required to experience 31-38 cases until the operation time for SSPT was stabilized. Special care should be exercised to prevent vascular damage in the vicinity of the innominate veins during the early stages after SSPT introduction.