Background <p>Less participation by Japan in multi-regional clinical trials (MRCTs) is one of concerns that leads to drug loss in Japan, but the characteristics of Japan’s participation in MRCTs have not been well studied.</p> Purpose <p>This study investigated Japan’s situation in global drug development by characterizing its participation in MRCTs compared with East and South-East Asian countries/regions, with a focus on MRCTs sponsored by small-medium companies to discuss necessary measures in further promoting drug development in Japan.</p> Methods <p>Data from MRCTs conducted in East and South-East Asia during the period from January 1, 2013 to December 31, 2022 were analyzed.</p> Results <p>Japan’s participation in MRCTs conducted in Asia (East Asia and South-East Asia) was limited. In particular, Japan participated in only 15–16% of MRCTs sponsored by Small/Medium-pharma (mainly US-based companies), with even less participation in Early Phase MRCTs. Japan’s participation in MRCTs was markedly lower than other Asian countries/regions such as Singapore, South Korea, and Taiwan, although it was relatively higher in MRCTs that targeted neoplasms compared with other diseases.</p> Conclusion <p>Results of this study raise significant concern about future potential drug loss in Japan. It is urgent to increase the participation of Japan in MRCTs in order to continuously provide new globally developed drugs to patients in Japan. For that purpose, an integrated approach that includes continuous improvement in pharmaceutical regulations and the clinical trial environment, as well as market attractiveness, will be necessary in parallel with strengthening of collaborations between Japan and other Asian countries/regions.</p>