We use single-particle tracking (SPT) to explore the role of nanoparticles/polymer interactions and polymer molecular weight on nanoparticle (NP) diffusion in unentangled polymer melts. The very dilute NP concentrations (similar to 10(-7) wt %) in SPT measurements enable tuning NP/polymer interactions so that the systems with unfavorable or neutral NP/polymer interactions in polymer melts can be studied without nanoparticle aggregation. Here, the diffusion coefficients of weakly interacting (methyl-capped, CH3 QDs) and strongly interacting (carboxylic acid-capped, COOH QDs) nanoparticles (radius = 6.6 nm) in poly(propylene glycol) (PPG) melts were measured via SPT. Mean-squared displacements and van Hove distributions of nanoparticle motion are consistent with Brownian motion of single nanoparticles in the long-time diffusion regime. The effective COOH QD size increases with PPG molecular weight as M-w(0.5), indicating a long-lived bound layer. However, for weakly interacting CH3 QDs, the effective nanoparticle radius is independent of PPG M-w due to the absence of a bound layer. In contrast to ensemble average methods (i.e., X-ray photon correlation spectroscopy), SPT methods directly detect spatial and temporal diffusion behavior of individual nanoparticles and provide previously inaccessible information about nanoparticle diffusion in polymer melts.