This study analyses the applicability of the recently released Level-3 (L3) daily and monthly aerosol optical depth (AOD) products (version F15_0032) over land retrieved from the Multiangle Imaging Spectroradiometer (MISR) instrument. For this purpose, daily AOD data from 427 Aerosol Robotic Network (AERONET) sites worldwide during 2001–2018 and 39 China Aerosol Remote Sensing Network (CARSNET) sites across China during 2002–2014 were selected for comparison. Also, MISR-based size-segregated AODs were collected to compare with the coarse- and fine-mode AODs retrieved from AERONET to reveal the particles size modes that mainly contribute to the offset of MISR total AOD relative to observations. By comparing with five other monthly AOD datasets, including two MODIS (Moderate resolution Imaging Spectroradiometer) retrieval products, a multi-satellite merged product, and two aerosol reanalysis, MERRA-2 (Modern-Era Retrospective Analysis for Research and Applications) and CAMS (Copernicus Atmosphere Monitoring Service), we then explored the applicability of MISR for characterizing the climatology, interannual variations, and long-term (2003–2017) trends in regional aerosol loadings over the 12 regions of interest. Overall, about 80% (60%) of the daily AOD values retrieved by MISR fall within expected error bounds of ± [0.05 + 0.2 × AOD] (±[0.03 + 0.1 × AOD]), with a high correlation (R = 0.87). Our comparison results show that although the V23 algorithm addresses several issues in L2 AOD retrieval relative to the previous version, the L3 data aggregated from L2 data tends to on average overestimate low AOD values and underestimate high AOD values. These offset relative to observations are mainly attributed to the overestimation of coarse-mode AOD and the underestimation of fine-mode AOD by MISR. Intercomparison of 2003–2017 AOD trends from multiple data sources indicate that MISR can capture well the increases occurring in South Asia, as well as the decreases occurring in Eastern China, Eastern United States, and Western Europe. Our study confirmed that MISR L3 product performs reliably at regional scales, particularly in typically polluted areas, but caution is still needed when applied to areas where sparse sampling is encountered.