Comayagua is worth visiting year-round, but the two best times are Semana Santa (Holy Week, March or April) for the famous alfombra processions, and the dry season (November to April) when the weather is most reliable.
The city sits at about 600 meters in a broad valley, giving it a warm but not oppressive climate — cooler than the coast, warmer than Tegucigalpa. The rainy season (May to October) brings afternoon downpours but rarely disrupts morning sightseeing.