Medvedev, who has received an opening-round bye in Madrid, said last month that clay was his least preferred surface and once again made his feelings clear during the second round match.
"I don't want to play here on this surface!" exclaimed Medvedev at a change of ends.
Medvedev, however, recovered from a mid-match blip to defeat Davidovich Fokina 4-6 6-4 6-2 in little over two hours.
Tsitsipas, Zverev stunned at Indian Wells as draw opens up for Norrie
At the end of the day, it was all love for the Russian, who signed off with "Love clay :)" on the TV camera following his first win on the surface since April 2019.
- Why is clay such a struggle for Medvedev? And can he improve?
- Norrie showing quality on clay - but how far can he go?
Medvedev has a slim chance to rise to the top of the world rankings this month if he captures the Madrid title, reaches at least the semi-finals in Rome and other results go his way.
But the 25-year-old still has winless records at both Rome and the French Open, which begins in Paris on May 30.
Elsewhere, Rafael Nadal wasn't in a giving mood as he beat birthday boy Carlos Alcaraz, who turned 18 on Wednesday, 6-1, 6-2 in their second round match.
Nadal beats birthday boy Alcaraz at Madrid Open
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