The world ranked no. 8, who played a doubles match with Kei Nishikori last weekend, will face Serbian Laslo Djere on Wednesday in his first singles tournament since the Delray Beach Open in February.
Del Potro suffered a knee injury in October last year and although he reached the semi-final of the Delray tournament, he was in obvious pain and took another break afterwards.
The decision to return comes less than three weeks before the French Open, a tournament in which he has never got past the semi-final.
However, four of Del Potro's 22 singles titles have come on clay, and the big Argentine will be aiming to return to form and add a second grand slam title to his 2009 win in the US Open.
(Reporting by Andrew Downie; Editing by Hugh Lawson)
