This study examines U.S. exports and imports to/from its major 15 trading partners and Russia. To analyze U.S. export and import flows the gravity model approach is used. Factors affecting U.S. bilateral trade flows with its 16 trading countries are evaluated using Generalized Method of Moments (GMM). Annual data from 2000 to 2009 are used for this study. Goods traded between the U.S. and its trading partners are disaggregated into three groups based on the Standard International Trade Classification (SITC). Results show that major factors affecting both U.S. export and import flows are distance and change in polity score. Also U.S. exports are influenced by U.S. trading partner Gross Domestic Product (GDP) for agricultural (AGR) and middle sector (MID) groups. U.S. foreign direct investment is a complement for U.S. exports of final (FIN) group and at the same time it serves as substitute for U.S. exports of AGR. On the other hand, U.S. imports of AGR and foreign direct investment (FDI) from 16 trading partners to the U.S. are substitutes. This study also reveals that the U.S. and Russia bilateral trade could be improved through economic growth in both countries, improving political cooperation and increasing inward and outward FDI.