The US and the EU are negotiating a comprehensive Trans-Atlantic Trade and Investment Partnership (TTIP). The main purposes of the agreement are to stimulate economic growth and employment, to facilitate trade and investment and raise competitiveness on both sides of the Atlantic. The US and EU are the biggest trade and investment partners for each other, as well as most important partners for a number of other countries. The Trans-Atlantic free trade agreement would not only facilitate bilateral cooperation, but has a potential to set up new, more advanced international trade and investment rules and practices. The agreement is aimed, among other point, at resolving some of the existing problems in bilateral relations, such as differences in regulatory practices, market access conditions, government procurement, intellectual property rights (IPR) and investor protection. However, some of these differences are deeply inherent in the regulatory systems and have become the reasons for numerous disputes. Despite the fact that the negotiations on TTIP are still in progress, it is already possible to identify and assess the underlying differences that would potentially hamper the creation of deep provisions in the future agreement. The paper aims at analyzing the most difficult areas of negotiations and giving predictions for the future provisions. Firstly, the paper gives an overview of the scope and structure of bilateral relations between the US and EU. Secondly, the authors give detailed analysis of the most important points of the negotiation’s agenda, making stress on the underlying differences in domestic regulation and assessing the depth of those differences. The conclusions are as follows. While some of the areas, such as tariffs, labor and environment, SMEs, state enterprises and others, are relatively easy to agree upon, as both economies are striving to achieve high standards, negotiations on other issues, such as government procurement, NTM regulation and IPR are less likely to achieve high standards.