The Optical Navigation Cameras (ONC-T, ONC-W1, ONC-W2) onboard Hayabusa2 are also being used for scientific observations of the mission target, C-complex asteroid 162173 Ryugu. Science observations and analyses require rigorous instrument calibrations. In order to meet this requirement, we have conducted extensive inflight observations during the 3.5 years of cruise after the launch of Hayabusa2 on 3 December 2014. In addition to the first inflight calibrations by Suzuki et al. (2018), we conducted an additional series of calibrations, including read-out smear, electronic-interference noise, bias, dark current, hot pixels, sensitivity, linearity, flat-field, and stray light measurements for the ONC. Moreover, the calibrations, especially flat-fields and sensitivities, of ONC-W1 and -W2 are updated for the analysis of the low-altitude (i.e., high-resolution) observations, such as the gravity measurement, touchdowns, and the descents for MASCOT and MINERVA-II payload releases. The radiometric calibration for ONC-T is also updated in this study based on star and Moon observations. Our updated inflight sensitivity measurements suggest the accuracy of the absolute radiometric calibration contains <1.8% error for the ul-, b-, v-, Na-, w-, and x-bands based on star calibration observations and ~5% for the p-band based on lunar calibration observations. The radiance spectra of the Moon, Jupiter, and Saturn from the ONC-T show good agreement with the spacecraft-based observations of the Moon from SP/SELENE and WAC/LROC and with ground-based telescopic observations for Jupiter and Saturn. Our calibration results suggest that the 0.7-μm absorption band typically observed on Ch and Cgh asteroids at the ~3–4% level can be detected with the ONC's signal-to-noise ratio (SNR) of ~2. We also demonstrate a decrease in SNR due to CCD temperature increases caused by radiant heat when the spacecraft is close to the surface, as the SNR is measured to be 150 at a CCD temperature of 20 °C (the worst case scenario). Since Ryugu may possess a significant amount of internal volatiles, a sodium atmosphere around Ryugu is considered to be highly plausible. We evaluated the upper limit of detectability of a sodium atmosphere around Jupiter using the Na-filter as 100 R with 100 images. This implies that the ONC-T can detect a sodium atmosphere of several 10s kR based on a single image set of v- and Na-bands and of several 100 s R based on 100 image sets. Finally, we report the first inflight observation of Ryugu by ONC-T from 1.3 × 10 6 km away on 26 February 2018. The ONC-T v-band photometric observation displays consistency with ground-based observation, which confirms the capability of ONC-T.