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Sayre dates to 1783, when a gristmill was built along Shepard Creek. Greater Sayre began around 1870 at a railroad junction near the Susquehanna River. Activity at that junction led to the community eventually named Sayre. Sayre experienced phenomenal growth with the expansion of the Lehigh Valley Railroad operations. Its reputation as a railroad town began to fade after World War II, ending with the demise of the railroad by the 1970s. In its place, Guthrie Healthcare now provides the strongest influence on the town. Today the hospital's position in Sayre is as important as the railroad was in its heyday, both serving as the keystones of a town that thousands call home.