Santa Clara's climate is typical of Cuba's interior: hot and humid from June to October, with the most rain between September and October; drier and more comfortable from November through April. The heat is slightly more intense than on the coast, since there's no sea breeze to moderate things.
The best time to visit is November through March. Temperatures are in the low to mid-20s Celsius, nights are cool enough for a light jacket, and the rain is rare. This is also when the city is most animated — the university is in full session, and the cultural calendar is full.
The anniversary of the battle of Santa Clara (29 December) is marked each year with ceremonies at the Tren Blindado and the Che Guevara Mausoleum. If you're interested in revolutionary history, this is a significant date. The university graduation season in June and July brings another surge of activity to the city.