Objective: In recent years, the medical applications of plasma activated water (PAW) have attracted growing interest. PAW can be prepared using plasma generated by hydrodynamic cavitation bubbles (HCB). To facilitate this application, the current study was performed to investigate the efficiency of plasma generation in HCB. Methods: Based on the plasma generated in HCB, an experimental system has been constructed. We measured the characteristics of the cavitating flow, including pressure, temperature, and water flow rate, and estimated the system and cavitation power consumptions. High-speed images of cavitating flow were obtained to examine the evolution of the cavitation zone. Images of discharge emission at various velocities were captured to identify the location of electrodes. In addition, optical emission spectra were examined to determine the type of reactive species. H2O2 concentration and energy efficiency were measured and analyzed. Results: In this experiment, the system power consumption was 1.2W. The highest cavitation power consumption was 50.4W and increased with the elevation of throat velocities. The processing findings of high-speed images revealed that the cavitation characteristic length was essential for plasma generation and was necessary for establishing the location of electrodes. In addition, the UV-Vis emission spectra of the plasma discharge demonstrated that the hydroxyl radical ·OH was formed in situ and that cavitation increased the yield of ·OH. H2O2 was the principal active component of PAW. Plasma generated in HCB produced H2O2 with a high energy efficiency of 77.0mol/kWh. Conclusion: Plasma generated in HCB may provide a viable and cost-effective alternative method for PAW preparation.