Background: Free flap survival relies on adequate tissue perfusion. We aim to give an overview of the available literature of all objective methods to intraoperatively assess free flap tissue perfusion, and the effects on (partial) flap loss. Methods: A systematic review and meta-analysis according to the PRISMA guidelines was performed (PubMed, Cochrane Library, Embase) regarding English language articles. Meta-analyses were performed by pooling means and slopes using random-effect models. Results: Sixty-four articles were included reporting on 2369 procedures in 2009 patients with various indications. Reported methods were fluorescence imaging (FI), laser Doppler, oxygen saturation, ultrasound, (dynamic) infrared thermography, venous pressure, and microdialysis. Intraoperative tissue perfusion was adequately measured by the use of FI and laser Doppler, leading to surgical intervention or altered flap design, and increased flap survival. Meta-analysis showed a mean time until onset of the dye to become visible of 18.4 (7.27; 29.46, Q P<0.001) sec. The relative intensity of the flap compared to the intensity curve of normal tissue was 75.92% (65.85; 85.98, Q P=0.719). The mean difference in the slope value of the oxygen tensions before and after the anastomosis was -0.09 (-0.12; -0;06 Q P=0.982). No convincing evidence was found for the use of other methods. Conclusions: Based on the current literature, FI and laser Doppler are most suitable to intraoperatively measure free flap tissue perfusion, resulting in improved flap survival. However, this review was limited by the available literature. Additional studies are necessary to investigate the predictive value of intraoperative perfusion measurement.