Introduction Local perforator flaps have become a standard procedure in reconstructive surgery. They allow the transfer of large tissue units with minimal donor-site morbidity. However, clinical studies on flap perfusion changes over time are lacking. The aim of this study was to investigate the perfusion of free-style single perforator flaps with an eccentrically located main perforator by combined laser Doppler spectrophotometry. Patients and methods Ten patients (six male, four female, 29-71 years) were included in this prospective clinical study. All flaps were based on one perforator. Flaps were harvested from the trunk (n = 6) or the proximal upper or lower extremity (n = 4). Flap perfusion was assessed using a combined laser Doppler spectrophotometry (CLDS) device (O2C, Oxygen to See, LEA Medizintechnik, Giessen, Germany) at days 0, 1, 7 and 14 in different zones. Results Flap dimensions were 18.6 ± 4.7 × 7.2 ± 1.6 cm. Two flaps developed minor tip necroses (<10%), eight flaps survived completely. CLDS proved to be very sensitive for the detection of regional perfusion problems. A considerable perfusion gradient was observed at days 0 and 1. Here, reduced blood flow and post-capillary oxygen saturations were found at the tip when compared to the region above main perforator (RAMP). Blood flow remained stable proximally while it improved significantly from day 1 to 14 at the tip region. Conclusion CLDS is an effective method for objective evaluation of flap perfusion. Although distal flap perfusion is diminished initially, the majority of perforator flaps with eccentrically located perforators survive completely. Obviously, flap perfusion improved between days 1 and 14. This clinical finding might be explained by reorganisation of the vascular system with opening of so-called connecting or choke vessels. This knowledge might influence decision making in perforator flap surgery.