Comayagua sits on the main highway between San Pedro Sula and Tegucigalpa, making it an easy stop on the way between the two cities. Direct buses from both cities run frequently and take 1.5-2 hours from Tegucigalpa and 2-3 hours from San Pedro Sula.
Palmerola International Airport (XPL) is located near Comayagua and handles international flights including connections to the United States. This makes Comayagua a possible first stop for visitors entering Honduras by air, rather than starting in Tegucigalpa. A taxi from the airport into the city center takes about 20 minutes.