This paper includes the results of a long-term monitoring of the thermal conditions in a selected number of office buildings in Kumasi, Ghana. The monitored data was not only used to evaluate indoor environmental conditions in these offices, but also to calibrate a number of thermal simulation models of the buildings. Thus, a simulation-based exploration of thermal retrofit options toward a general reduction of cooling requirements could be conducted. Moreover, the impact of thermal retrofit measures toward reducing carbon dioxide (CO2) emissions was assessed and the amortization times for investments in such retrofit measures were estimated. The results suggest that improvements in building fabric and controls (with payback times of 3 to 12 years) can reduce buildings' cooling loads around 20% to 35% and CO2 emissions around 27%.