Devices, systems, and methods for more efficiently ablating tissue with pulsed field ablation energy while minimizing collateral injury to non-target tissue. In one embodiment, a system for ablating tissue at a treatment site comprises: an energy delivery device； and a control unit including: a source of impedance-modifying fluid in fluid communication with the energy delivery device； an energy generator in electrical communication with the energy delivery device, the energy generator being configured to transmit energy to the energy delivery device and the energy delivery device being configured to deliver energy to the treatment site； and processing circuitry configured to control delivery of the impedance-modifying fluid from the energy delivery device to the treatment site. In one embodiment, a method for ablating tissue comprises delivering an impedance-modifying fluid to a treatment site and delivering pulsed field ablation energy to the treatment site.
