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| 1st(1st leg) | América de Cali | - | Unión Magdalena | 1:2 (1:2) | ||
| 2nd (2nd leg) | Unión Magdalena | - | América de Cali | 2:1 (2:1) | ||
| 1st(1st leg): 20/04/2022 21:30 | 2nd (2nd leg): 12/05/2022 15:00 | Winner: Unión Magdalena | ||||
| 1st(1st leg) | Independiente Medellín | - | Tigres FC | 1:0 (1:0) | ||
| 2nd (2nd leg) | Tigres FC | - | Independiente Medellín | 1:2 (1:0) | ||
| 1st(1st leg): 20/04/2022 21:30 | 2nd (2nd leg): 11/05/2022 20:00 | Winner: Independiente Medellín | ||||
| 1st(1st leg) | La Equidad | - | Atlético Bucaramanga | 2:0 (2:0) | ||
| 2nd (2nd leg) | Atlético Bucaramanga | - | La Equidad | 0:0 (0:0) | ||
| 1st(1st leg): 20/04/2022 22:00 | 2nd (2nd leg): 11/05/2022 23:00 | Winner: La Equidad | ||||
| 1st(1st leg) | Atlético Junior | - | Santa Fe | 2:1 (1:1) | ||
| 2nd (2nd leg) | Santa Fe | - | Atlético Junior | 0:1 (0:0) | ||
| 1st(1st leg): 21/04/2022 00:00 | 2nd (2nd leg): 12/05/2022 02:10 | Winner: Atlético Junior | ||||
| 1st(1st leg) | Deportes Tolima | - | Deportivo Pereira | 3:2 (2:2) | ||
| 2nd (2nd leg) | Deportivo Pereira | - | Deportes Tolima | 1:1 (0:1) | ||
| 1st(1st leg): 21/04/2022 01:30 | 2nd (2nd leg): 12/05/2022 01:00 | Winner: Deportes Tolima | ||||
| 1st(1st leg) | Atlético Nacional | - | Once Caldas | 3:0 (2:0) | ||
| 2nd (2nd leg) | Once Caldas | - | Atlético Nacional | 1:2 (0:1) | ||
| 1st(1st leg): 21/04/2022 02:00 | 2nd (2nd leg): 12/05/2022 00:00 | Winner: Atlético Nacional | ||||
| 1st(1st leg) | Deportivo Cali | - | Fortaleza FC | 1:3 (1:1) | ||
| 2nd (2nd leg) | Fortaleza FC | - | Deportivo Cali | 1:1 (0:1) | ||
| 1st(1st leg): 21/04/2022 02:15 | 2nd (2nd leg): 13/05/2022 02:00 | Winner: Fortaleza FC | ||||
| 1st(1st leg) | Millonarios | - | Jaguares de Córdoba | 3:0 (2:0) | ||
| 2nd (2nd leg) | Jaguares de Córdoba | - | Millonarios | 1:1 (1:1) | ||
| 1st(1st leg): 22/04/2022 02:00 | 2nd (2nd leg): 12/05/2022 00:00 | Winner: Millonarios | ||||
