Hydroxyl (OH) and hydroperoxyl (HO₂) drive the atmosphere’s oxidation of gases emitted from Earth’s surface and the formation and aging of aerosol particles. Thus, understanding OH and HO₂ chemistry is essential for examining the impact of human activity on future atmospheric composition and climate. Using the OH and HO₂ dataset collected with the Penn State Airborne Tropospheric Hydrogen Oxides Sensor (ATHOS) during nine aircraft missions over the past 20 years, we compare observed OH and HO₂ to that modeled using the same near-explicit photochemical box model. In general, the agreement is well within the uncertainties of the observations and models, even when the model is constrained only with a common data set of simultaneous measurements. However, in regions influenced by anthropogenic or biogenic volatile organic compounds, the model chemical mechanism and size of the data set of constraining measurements do matter. In cleaner regions, the differences between observed and modeled OH and HO₂ found in previous studies generally remain and do not appear to be systematic, indicating that the differences are driven by measurement issues for ATHOS and/or other instruments. Thus, these comparisons indicate that the oxidation chemistry in most of the free troposphere is understood to as well as current measurements can determine. The focus of future research needs to be on regions rich in volatile organic compounds, where observed-to-modeled differences are more persistent, and on improving measurement consistency.