The purpose of this study was to develop and test a novel mode of negative pressure wound therapy (NPWT) that minimises pain while preserving the efficacy in wound healing. A porcine model was used in this study. Wounds were generated in animals and treated with either simple dressing or various treatment modes of NPWT. The wound volume, perfusion level and vasculature status were analysed and compared among different groups. Clinical application was performed to evaluate the level of pain occurring when negative pressure is applied. Among the NPWT groups, the Cyclic-50 group showed most decrement in wound volume, even though statistical relevance was not found (P = 0·302). The perfusion level was significantly increased in the Cyclic-50 group compared with the Intermittent group (P < 0·001) and the Cyclic-100 group (P = 0·004). Evaluation of blood vessel formation revealed that the Cyclic-50 group showed the highest number of vasculature with statistical significance (P < 0·001). In clinical application, the cyclic group showed significant decrease in pain compared with the intermittent group (P = 0·001). The cyclic NPWT mode decreased patient discomfort while maintaining superior wound healing effects as the intermittent mode.