The General Court of the European Union has overturned a ruling stating that Apple should pay almost $15 billion in tax to the Irish Government. Vestager has also tried to reel in American tech companies in matters of competition and privacy.
But the courts countered the Commission's claims, saying that "although the General Court regrets the incomplete and occasionally inconsistent nature of the contested tax rulings, the defects identified by the Commission are not, in themselves, sufficient to prove the existence of an advantage".
"The Commission will continue to look at aggressive tax planning measures under European Union state aid rules to assess whether they result in illegal state aid", she said, following the ruling.
The Commission's decision concerned two tax rulings issued by Ireland to Apple, which determined the taxable profit of two Irish Apple subsidiaries in Ireland between 1991 and 2015.
In many cases, multinationals can pay taxes on the bulk of their revenue across the EU's 27 countries in the one European Union country where they have their regional headquarters.
The Commission has two months to appeal the decision at the European Court of Justice - the bloc's highest court - on points of law only. An earlier Apple statement said that the case "was not about how much tax we pay, but where we are required to pay it".
The company added that it "has paid more than $100 billion in corporate income taxes around the world in the last decade and tens of billions more in other taxes". The Commission concluded that Cupertino, California-based Apple used two shell companies incorporated in Ireland to permit Apple to report its Europe-wide profits at effective rates well under 1 percent.
The ruling is a setback to the Commission's fight - led by Vestager - to reduce the practice of profit shifting whereby multinational companies shift profits from a high tax jurisdiction to a lower one.
Wednesday's decision by the EU's general court is a significant blow for the EU's executive arm in its campaign to stymie profit-shifting by multinationals and limit the power of USA big tech.
The cases are: T-778/16, Ireland v. Commission, T-892/16, Apple Sales International and Apple Operations Europe v. Commission.
Ireland appealed the Commission's order with Apple, but many commentators said it stood to lose whatever the outcome.
Ireland has already changed laws to deal with issues in relation to company residency and has made necessary legislative changes as global tax rules have changed over time, the Minister said. Some EU countries are looking to impose a tax on major digital businesses.