Single-crystalline Ag2Se nanowires have been successfully synthesized through a template-engaged topotactic reaction in which nanowires of trigonal selenium were transformed into Ag2Se by reacting with aqueous AgNO3 solutions at room temperature (RT). An interesting size-dependent transition between two crystal structures has also been observed for this newly synthesized one-dimensional system: The Ag2Se nanowires adopted a tetragonal structure when their diameters were less than similar to40 nm. Since this reaction can be carried out at ambient pressure and temperature, it should be straightforward to scale up the entire process for the high-volume production of Ag2Se nanowires with well-controlled sizes and crystal structures. These highly uniform nanowires of single-crystalline Ag2Se are potentially useful as photosensitizers, superionic conductors, magnetoresistive compounds or thermoelectric materials. This work also represents the first demonstration of a template-engaged process capable of generating single-crystalline nanowires from the solution-phase and at RT.