"I take this miserable and vile attack as recognition of my status as an anti-imperialist revolutionary," El Aissami, the heir apparent to Socialist President Nicolas Maduro, wrote on Twitter.
The US Treasury Department on Monday accused El Aissami and an ally, businessman Samark Jose Lopez Bello, of being major cocaine traffickers and froze their US assets.
It said El Aissami protected and oversaw large shipments of drugs from Venezuela to Mexico and the United States while serving as the country's interior minister and governor of Aragua state.
"Let's not let these vile provocations distract us. Our main job is to accompany Nicolas Maduro in (Venezuela's) economic recovery," El Aissami tweeted.
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"We must concentrate on the revolutionary government's priorities: economic recovery and growth and guaranteeing PEACE and social happiness."
He added a shout-out to late leftist firebrand Hugo Chavez, Maduro's predecessor and the man who launched Venezuela on the path of socialist "revolution" -- and a diplomatic collision course with the "imperialist" United States -- in 1999.
The US sanctions cast a dark shadow over El Aissami, 42, who became the troubled South American country's vice president on January 4. El Aissami, who was born in Merida state, served as a minister under Chavez.