The 2022 Open Città della Disfida was a professional tennis tournament played on clay courts. It was the 22nd edition of the tournament which was part of the 2022 ATP Challenger Tour. It took place in Barletta, Italy between 11 and 17 April 2022.
| Country | Player | Rank1 | Seed | |
|---|---|---|---|---|
 France | Gilles Simon | 136 | 1 | |
| Nuno Borges | 143 | 2 | ||
 Czech Republic | Zdeněk Kolář | 150 | 3 | |
 Austria | Jurij Rodionov | 162 | 4 | |
 Italy | Franco Agamenone | 167 | 5 | |
| France | Enzo Couacaud | 179 | 6 | |
| France | Constant Lestienne | 188 | 7 | |
 Poland | Kacper Żuk | 189 | 8 |
The following players received wildcards into the singles main draw:
The following players received entry into the singles main draw as alternates:
The following players received entry from the qualifying draw:
See main article: 2022 Open Città della Disfida – Singles.
Miljan Zekić 6–3, 7–5.See main article: 2022 Open Città della Disfida – Doubles.
Ben McLachlan / Szymon Walków 6–3, 6–4.