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Bhutan locates in a high seismicity region but has no seismic design code of its own. Recent devastating earthquake in Nepal, which is located in the same region as Bhutan and with similar construction types, raises the concern on the seismic safety of building structures in Bhutan. This study is aimed at assessing the performance of masonry-infilled and soft storey reinforced concrete frame buildings in Bhutan under the 475- and 2475-year return period ground motions predicted from the Probabilistic Seismic Hazard Analysis. A nonlinear strut model is used to model the infill wall, and the influence of openings and soil–structure interaction are considered in the analyses. The result suggests that the masonry-infilled reinforced concrete frame buildings in Bhutan could suffer repairable and irreparable damages under the 475-year return period ground motions and severe damages and even collapse under the 2475-year return period ground motion. The buildings with the soft storey are found to be more vulnerable than the normal masonry-infilled reinforced concrete buildings. The design recommendation of Indian Seismic Code improves the performance of soft storey buildings but cannot fully negate the soft storey effect. This study is the first such effort in assessing the performance of general building stocks in the high seismicity Bhutan. The results can guide the seismic strengthening options and can be used for further loss predictions for seismic preparedness of the country.