The oxygen volumetric mass transfer coefficient is a key parameter to characterize the performance of aerobic bioreactors. A novel rotating-drum bioreactor (RDB) fitted with a sparger as proposed in a previous work has demonstrated its excellent gas-liquid mass transfer performance. To provide primary information on the design and scale-up of the novel RDB, effects of reactor configuration including the number and width of lifters and operation conditions such as rotational speed, aeration rate, and solid volume fraction on mass transfer performance were systematically investigated in a new medium-sized RDB. Compared with the stirred bioreactor and traditional RDBs, this new RDB exhibits better mass transfer performance. Taking both operational and reactor configuration parameters into consideration, an empirical correlation to predict the volumetric mass transfer coefficient in this type of RDBs was proposed which is valuable for its design and scale-up.