The silver-indium system has become important in electronic packaging applications. The In-3.5 % Ag eutectic alloy has been used for laser diode attachment since 1980. The Ag-rich alloys were less studied but have received significant attention recently for producing high temperature joints at low bonding temperature. In multilayer Ag-rich bonding structure design, typical bonding temperature is 180 °C and the process can be made entirely fluxless. The melting temperature of joints fabricated is higher than 695 °C. Despite success in several bonding processes, the chemical reactions of Ag and In at 180 °C were little known. In this study, we performed systematic experiments to investigate these reactions. In experimental design, copper (Cu) substrates were electroplated with 40 μm Ag layer, followed by indium layers of 1, 3, 5, 10, and 15 μm, respectively. Thick Ag layer was chosen to prevent In from reacting with the Cu substrate. The samples were annealed at 180 °C in 0.1 torr vacuum for 5 min to emulate the bonding conditions. The microstructure and composition on the surface of the samples were evaluated using scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDX) as well as X-ray diffraction. They were then cut in cross section, polished, and examined by SEM/EDX. The results show that, for samples with 1 μm thick In, the In layer converts to Ag2In entirely after annealing. For samples with In thickness of 3 and 5 μm, AgIn2, Ag2In, and solid solution (Ag) all form after annealing. No indium was identified. For samples having 10 and 15 μm thick In, In covers almost over the entire sample surface after annealing. The effect of annealing Ag layer was investigated. After Ag plating, samples were annealed at 450 °C for 3 h to grow Ag grains. This was followed by plating 10 μm In and annealing at 180 °C. The result shows that, by annealing Ag before plating In, more In is kept in the structure during annealing at 180 °C. In theory, this effect is caused by larger Ag grains and thus fewer grain boundaries resulting from annealing the Ag layer. Other than scientific values, the results of this investigation are useful in designing better bonding structures.