Embodiments of negative pressure wound therapy systems and methods for operating the systems are disclosed. In some embodiments, a system includes a pump assembly, canister, and a wound dressing configured to be positioned over a wound. The pump assembly, canister, and wound dressing can be fluidically connected to facilitate delivery of negative pressure to the wound. The system can be configured to deliver negative pressure based at least on a sensed pressured in a fluid flow path connecting a pump of the pump assembly and the wound dressing. The sensed pressure can be sampled, in some embodiments, synchronous with operation of the pump and can be used for controlling the pump. Increased efficiency, diminished noise and vibration caused by operation of the pump, reduced in energy usage, and better comfort for the patient can be attained.