He did research and later became a professor at the Department of Medicine, where he specialised in microbiology and immunology.

He is one of the founders and the second president of the International Society for Antiviral Research.

[1]: 6–7 [2][3]: 3, 23 Since 1976 Erik De Clercq has collaborated on the development of new antiretroviral drugs with Antonín Holý, of the Institute of Organic Chemistry and Biochemistry (IOCB Prague) of the Czechoslovak Academy of Sciences in Prague, Czech Republic.

In 2008 he received the European Inventor Award Lifetime Achievement for landmark contributions to antiviral treatment, including the development of the drug cocktail for AIDS.

He was recognized for his landmark discoveries in anti-HIV medications, including nucleotide analogues, and inventions or co-inventions of several approved drugs for anti-viral therapy.