The short shelf-life of water-soluble quantum dots (QDs) due to colloidal instability represents a major drawback to their exploitation. This work examines the colloidal stability of PbS nanoparticles capped with dihydrolipoic acid-polyethylene glycol (DHLA-PEG) ligands terminated with functional groups such as -NH2, -COOH, OMe and -N3. and their application for in vivo imaging. We prove a mechanism of colloidal instability and develop a strategy to produce for the first time stable PEG-capped PbS quantum dots with high quantum yield and optical emission in the first and the second near-infrared (NIR) windows of low absorption of biological tissues. The NIR imaging of in vivo biodistribution is demonstrated at wavelengths >1000 nm, with benefits of reduced tissue absorption and light scattering. The stability, biocompatibility and potential for further QD functionalization open up realistic prospects for non-invasive bioimaging applications.