In this study, hydrodynamic parameters and mass transfer characteristics were measured at four acetaminophen concentrations (1000–4000 mg/l) in water over the range of superficial gas velocity of 0.2–1 cm/s at 25 °C in a split-cylinder airlift bioreactor. The gas hold-up and overall oxygen transfer coefficient for all the fluids increased with increasing the gas velocity. The specific interfacial area increased and liquid-side oxygen transfer coefficient decreased with increasing gas velocity. Furthermore, the gas hold-up increased and bubble diameters decreased with acetaminophen addition. The overall oxygen transfer coefficient and gas hold-up increased and bubble diameter decreased with increasing acetaminophen concentration. The overall oxygen transfer coefficient increased due to increasing the specific interfacial area (with surface tension and bubble size reduction). Two correlations based on the dimensionless numbers were developed to find Sherwood number and gas hold-up.