Removal of contaminants of emerging concern (CECs) from municipal wastewater is becoming more and more important. On-site regeneration of exhausted adsorbents can be the key to practical applications. In this study, ozone-based regeneration of granular zeolites loaded with acetaminophen (ACE) was investigated. The adsorption capacity of ACE was 90 mg/g. After adsorption and breakthrough in column tests, granular zeolites were drained and dried for regeneration. Water content in granules is the main factor that limits the regeneration performance by affecting the gaseous ozone transfer rate. Ozone-based regeneration of fully dried granular zeolites (0% water content) is the most efficient, whereas fully wet granules (40% water content) have poor regeneration efficiency. Various ozone concentrations and gas flow rates were applied. With the same total mass of ozone dosed (900 mg), the regeneration efficiency increased by increasing the ozonation duration up to 50 min. The longer the regeneration time, the deeper the gaseous ozone can diffuse into the inner pores of zeolites to decompose the adsorbed ACE. The effect of gaseous ozone on the adsorption capacity of zeolites and the effect of the intermediates accumulation on the long-term adsorption capacity recovery rate were also investigated. It was found that gaseous ozone did not influence the adsorption of ACE on zeolites. The adsorption capacity of ACE decreased 7% after three adsorption-regeneration cycles. This can be explained by the accumulation of undissolved intermediate breakdown products adsorbed on the granules.