This paper reports a facile aqueous-based synthesis method for highly luminescent Ag nanoclusters (NCs) with tunable emissions. The key strategy was to use a reduction-decomposition-reduction cycle to modify the Ag NC intermediates that were further subjected to size/structure focusing. The as-modified Ag NC intermediates were more robust in water against the subsequent etching by thiol ligands, making a mild size-/structure-focusing environment possible, which produced highly luminescent Ag NCs with a well-defined size and structure. Ag NCs with intense red and green emission were successfully synthesized by this method. These Ag NCs possessed a well-defined size and structure (Ag 16 (SG) 9 and Ag 9 (SG) 6 ), and exhibited excellent stability in the aqueous phase. Our highly luminescent Ag NCs also possessed superior antimicrobial properties against the multidrug-resistant bacteria Pseudomonas aeruginosa, via generating a high concentration of intracellular reactive oxygen species. Keywords: antimicrobial; biomedical applications; luminescence; silver nanoclusters; thiol ligands INTRODUCTION Ultrasmall noble metal nanoclusters (NCs), typically composed of several to a hundred metal atoms, present unique physical and chemical properties between single atoms and large nanocrystals (42 nm). [1][2][3][4] Owing to the strong quantum size confinement in this size range (o 2 nm), NCs possess discrete and size-tunable electronic transitions and display unique molecule-like properties, such as quantized charging and luminescence. [5][6][7][8][9][10][11][12] Strong luminescence is one of the most attractive features of these NCs owing to their ultrafine size, good photostability and low toxicity; 13 some of these properties may not be realized by other luminophores, such as organic dyes (for example, photostability concerns) and semiconductor quantum dots (for example, relatively large size and toxicity concerns). 2,8,9,14,15 Recent studies have shown that luminescent Au and Ag NCs are promising optical probes for bioimaging and biosensing applications. 4,[16][17][18][19][20] This finding has led to the development of various methods for the synthesis of highly luminescent Au and Ag NCs. 2,21 On the other hand, insofar as nanostructured Ag-based materials are concerned, they are finding an increasing usage for antimicrobial applications owing to the unique chemistry of Ag interfacing with microorganisms. [22][23][24] Although there is a large volume of work exploring the potential use of large Ag