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"Trump: a racist and fascist gringo," read one of the placards held up, depicting the US leader dressed as the devil.
The annual parade, held by students of San Carlos University, is a 119-year-old tradition meant to satirically foreshadow more conventional marches held a week later, during the pre-Easter Semana Santa holiday period.
In recent years, it has focused on corruption and pervasive violence in Guatemala, and on President Jimmy Morales's government.
A tragic fire in a children's shelter last month that killed 41 girls was one major theme among a slew of complaints this year. But Trump was a favored target.
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"Poverty and joblessness can't be held back with walls," another placard read, combining domestic complaints with Trump's plan to build a wall along the US-Mexican border to keep out undocumented migrants.