The aim of this study was to validate in vivo the accuracy of a reconstruction-based partial volume correction (PVC), which takes into account the point spread function of the imaging system. The NEMA NU2 Image Quality phantom and five healthy volunteers (using [(11)C]flumazenil) were scanned on both HR+ and high-resolution research tomograph (HRRT) scanners. HR+ data were reconstructed using normalization and attenuation-weighted ordered subsets expectation maximization (NAW-OSEM) and a PVC algorithm (PVC-NAW-OSEM). HRRT data were reconstructed using 3D ordinary Poisson OSEM (OP-OSEM) and a PVC algorithm (PVC-OP-OSEM). For clinical studies, parametric volume of distribution (V(T)) images were generated. For phantom data, good recovery was found for both OP-OSEM (0.84 to 0.97) and PVC-OP-OSEM (0.91 to 0.98) HRRT reconstructions. In addition, for the HR+, good recovery was found for PVC-NAW-OSEM (0.84 to 0.94), corresponding well with OP-OSEM. Finally, for clinical data, good correspondence was found between PVC-NAW-OSEM and OP-OSEM-derived V(T) values (slope: 1.02+/-0.08). This study showed that HR+ image resolution using PVC-NAW-OSEM was comparable to that of the HRRT scanner. As the HRRT has a higher intrinsic resolution, this agreement validates reconstruction-based PVC as a means of improving the spatial resolution of the HR+ scanner and thereby improving the quantitative accuracy of positron emission tomography.