Nanofiber mats and scaffolds have been widely investigated for biomedical applications. Commonly fabricated using electrospinning, nanofibers are generated ex situ using an apparatus that requires high voltages and an electrically conductive target. We report the use of solution blow spinning to generate conformal nanofiber mats/meshes on any surface in situ, utilizing only a commercial airbrush and compressed CO2. Solution and deposition conditions of PLGA nanofibers were optimized and mechanical properties characterized with dynamic mechanical analysis. Nanofiber mat degradation was monitored for morphologic and molecular weight changes in vitro. Biocompatibility of the direct deposition of nanofibers onto two cell lines was demonstrated in vitro and interaction with blood was qualitatively assessed with scanning electron microscopy. A pilot animal study illustrated the wide potential of this technique across multiple surgical applications, including its use as a surgical sealant, hemostatic, and buttress for tissue repair.