Omai is a high tonnage, low-grade, world-class gold deposit located in the Paleoproterozoic Guiana Shield. It is the second most important gold deposit in the Guiana Shield (after Las Cristinas, Venezuela), and one of the largest in South America (4.0 million oz.). Sm-Nd and Sr isotope data are presented for host rocks and for scheelite from auriferous quartz-carbonate-scheelite-sulfide-telluride veins from the Omai deposit. Gold-bearing veins are hosted by the Paleoproterozoic Barama-Mazaruni Supergroup, a greenstone belt sequence consisting of mafic volcanic rocks interbedded with sedimentary rocks that are intruded by quartz-feldspar porphyry and rhyolite dikes. This lithologic sequence was folded and metamorphosed to lower greenschist facies during the Paleoproterozoic Trans-Amazonian orogeny. The volcano-sedimentary unit was intruded by a post-tectonic quartz monzodiorite-diorite-hornblendite stock. Initial Nd isotope ratios for the Omai volcanic rocks range from ɛNd=+2.1 to +4.2. These values suggest that this part of the Guiana Shield was a site of new crust formation during the Paleoproterozoic and was not contaminated by older (Archean), reworked continental crust. Initial Nd isotope ratios for the Omai stock range between +0.5 and +2.3, which suggest limited contamination with previously formed continental crust. Although the Nd isotopic ratios of gold-related scheelites overlap with those of the host rocks, particularly the tholeiitic basalts at the interpreted time of vein emplacement, the lack of both isotopic mixing and significant Nd movement during the hydrothermal process suggest that the Nd isotope composition can be used to determine the isotopic characteristics of the ore fluid source area. At Omai, the ore fluid is largely derived from a radiogenic Nd source, represented by mantle or lower crustal reservoirs. Strontium isotope ratios for the scheelites cluster tightly between 0.7019 and 0.7021. The Sr isotope data suggest that unlike Nd, Sr was significantly mobile during the hydrothermal process. The fluids responsible for the Omai deposit may have picked up Sr along the flow path. The constant low Sr isotope values of scheelites probably reflect the key role that the local tholeiitic basalts played as the main source of Sr in the fluids. Whereas Nd isotopes identify the fluid source area, the Sr isotopes map the fluid flow paths.