The transport sector in Latin America accounts for over one-third of CO2 emissions. Shifting passengers from private vehicles to high capacity public transit has been identified as critical to relieve congestion and decarbonize transport, and switching to cleaner bus technologies can provide additional benefits in mitigating greenhouse gas emissions while reducing noise and air pollution. The uptake of clean bus technologies in Latin America and the Caribbean is slower than in China, Europe, and the U.S.A. This paper focuses on deepening understanding of the financial barriers to adopting clean bus technologies by developing a cost-effectiveness analysis that (i) assesses the marginal cost of reducing an additional ton of CO2 when switching from diesel buses to clean bus options and (ii) identifies the main drivers that determine this cost. The methodology has been applied to Santiago, the capital city of Chile, and results show that, given the current context, compressed natural gas is not a cost-efficient option for this city, while both hybrid electric and electric buses are already a cost-efficient option to mitigate climate change.