Recent studies, using modalities other than laser Doppler, have indicated that perfusion during negative-pressure wound therapy (NPWT) is reduced, contrary to world literature. The aim of the present study was to evaluate whether the measuring technique of the laser Doppler could be influenced by the compressive nature of NPWT dressings and whether this could explain the conflicting findings. A hypothesis that it may be possible for laser Doppler to record similar readings to those obtained during NPWT by merely compressing tissues manually was tested on 12 NPWT dressings, with each undergoing an alternating series of manual compressive forces and NPWT (−125 mmHg). During the periods of NPWT (n = 12), the mean perfusion recording increased in five experiments, reduced in six, and remained unchanged in one. During the period when manual pressure was applied (n = 12), there was a mean increase in perfusion in six experiments and a reduction in six. The type of change in perfusion (increase or decrease) was the same for both NPWT and manual pressure in 10 of the 12 experiments. In conclusion, laser Doppler can incorrectly record increased perfusion when tissues are compressed, implying that it is flawed in the field of NPWT research as tissues are always compressed to some degree by the NPWT dressing.