The second phase of Copa Sudamericana 2011 was the stage at which the biggest sides joined the competition. 8 Brazilians sides and six Argentine sides entered at this stage as well as the top seeded clubs from the other eight nations.
The first four ties to be completed were the ones featuring Brazilian sides. São Paulo came back from a 2-1 defeat in their first leg against Ceará to win the tie 4-2 on aggregate. Botafogo won both of their ties against Atlético Mineiro to progress to the next stage, Flamengo also cruised through their tie against Atlético Paranaense winning both legs 1-0 and Vasco Da Gama managed to scrape through on away goals against Palmeiras.
Of the Argentine sides two of the three ties were won by the underdogs. Arsenal de Sarandí, the minnows that won Copa Sudamericana in 2007 overcame Estudiantes and Godoy Cruz (a team that has never won a major trophy) eliminated Lanús on the away goals rule. Reigning Argentine champions Vélez Sársfield struggled in their first leg against Argentinos Juniors but progressed thanks to a thumping 4-0 win in their home leg. These three Argentine sides will be joined in the quarter finals by Independiente, who received a bye as reigning champions.
|Winner: São Paulo|
|Vasco Da Gama||2-0||Palmeiras|
|Palmeiras||3-1||Vasco Da Gama|
|Winner: Vasco Da Gama (on away goals)|
|Winner: Godoy Cruz (on away goals)|
|Argentinos Juniors||0-0||Vélez Sársfield|
|Vélez Sársfield||4-0||Argentinos Juniors|
|Winner: Vélez Sársfield|
|Universidad Cátolica||2-1||Municipal Iquique|
|Municipal Iquique||0-0||Universidad Cátolica|
|Winner: Universidad Cátolica|
|Universidad de Chile||1-0||Nacional|
|Nacional||SUSPENDED||Universidad de Chile|
|Winner: LDU Quito|
|Santa Fe||1-1||Deportivo Cali|
|Deportivo Cali||1-1||Santa Fe|
|Winner: Santa Fe (on penalties)|