The great Lisbon earthquake of November 1st, 1755 with an estimated moment magnitude of 8.5-9.0 was the most destructive earthquake in European history. The associated tsunami run-up was reported to have reached 5-15??m along the Portuguese and Moroccan coasts and the run-up was significant at the Azores and Madeira Island. Run-up reports from a trans-oceanic tsunami were documented in the Caribbean, Brazil and Newfoundland (Canada). No reports were documented along the U.S. East Coast. Many attempts have been made to characterize the 1755 Lisbon earthquake source using geophysical surveys and modeling the near-field earthquake intensity and tsunami effects. Studying far field effects, as presented in this paper, is advantageous in establishing constraints on source location and strike orientation because trans-oceanic tsunamis are less influenced by near source bathymetry and are unaffected by triggered submarine landslides at the source. Source location, fault orientation and bathymetry are the main elements governing transatlantic tsunami propagation to sites along the U.S. East Coast, much more than distance from the source and continental shelf width. Results of our far and near-field tsunami simulations based on relative amplitude comparison limit the earthquake source area to a region located south of the Gorringe Bank in the center of the Horseshoe Plain. This is in contrast with previously suggested sources such as Marqu??s de Pombal Fault, and Gulf of C??diz Fault, which are farther east of the Horseshoe Plain. The earthquake was likely to be a thrust event on a fault striking ~ 345?? and dipping to the ENE as opposed to the suggested earthquake source of the Gorringe Bank Fault, which trends NE-SW. Gorringe Bank, the Madeira-Tore Rise (MTR), and the Azores appear to have acted as topographic scatterers for tsunami energy, shielding most of the U.S. East Coast from the 1755 Lisbon tsunami. Additional simulations to assess tsunami hazard to the U.S. East Coast from possible future earthquakes along the Azores-Iberia plate boundary indicate that sources west of the MTR and in the Gulf of Cadiz may affect the southeastern coast of the U.S. The Azores-Iberia plate boundary west of the MTR is characterized by strike-slip faults, not thrusts, but the Gulf of Cadiz may have thrust faults. Southern Florida seems to be at risk from sources located east of MTR and South of the Gorringe Bank, but it is mostly shielded by the Bahamas. Higher resolution near-shore bathymetry along the U.S. East Coast and the Caribbean as well as a detailed study of potential tsunami sources in the central west part of the Horseshoe Plain are necessary to verify our simulation results. ?? 2008 Elsevier B.V.