Quantification of regional terrestrial carbon dioxide (CO2) fluxes is critical to our understanding of the carbon cycle. We evaluate inverse estimates of net ecosystem exchange (NEE) of CO2 fluxes in temperate North America, and their sensitivity to the observational data used to drive the inversions. Specifically, we consider the state-of-the-science CarbonTracker global inversion system, which assimilates (i) in situ measurements (’IS’), 29 (ii) the Orbiting Carbon Observatory-2 (OCO-2) v9 column CO 2 (XCO2) retrievals over land (’LNLG’), (iii) OCO-2 v9 XCO 2 retrievals over ocean (’OG’), and (iv) a combination of all these observational constraints (’LNLGOGIS’). We use independent CO2 observations from the Atmospheric Carbon and Transport (ACT)-America aircraft mission to evaluate the inversions. We diagnose errors in the flux estimates using the differences between modeled and observed biogenic CO2 mole fractions, influence functions from a Lagrangian transport model, and root-mean-square error (RMSE) and bias metrics. The IS fluxes have the smallest RMSE among the four products, followed by LNLG. Both IS and LNLG outperform the OG and LNLGOGIS inversions with regard to RMSE. Regional errors do not differ markedly across the four sets of posterior fluxes. The CarbonTracker inversions appear to overestimate the seasonal cycle of NEE in the Midwest and Western Canada, and overestimate dormant season NEE across the Central and Eastern US. The CarbonTracker inversions may overestimate annual NEE in the Central and Eastern US. The success of the LNLG inversion with respect to independent observations bodes well for satellite-based inversions in regions with more limited in situ observing networks.