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Smaller anastomotic coupling devices may increase the risk of complications in free flap reconstructions; however, the relationship between coupler size and venous thrombosis rates has not been adequately evaluated. The authors hypothesized that smaller diameter coupling devices are associated with higher rates of venous thrombosis than larger diameter devices in free tissue transfer.The authors reviewed a prospectively maintained database for all patients who underwent microsurgical free tissue transfer at their institution from 2001 to 2013. The primary outcome measured was venous thrombosis, and the primary objective was to assess the relationship between venous coupler diameter and the rate of venous thrombosis. The secondary objective was to compare venous thrombosis rates between coupled and hand-sewn venous anastomoses.A total of 5643 consecutive free flap reconstructions were evaluated; 3257 (57.7 percent) had coupled venous anastomoses. The 1.5-mm-diameter coupler had an overall thrombosis rate of 6.9 percent, significantly higher than that of all other coupler sizes (p = 0.04). In multivariable regression with generalized estimating equations analysis, both use of a 1.5-mm coupler (OR, 7.75; 95 percent CI, 3.20 to 18.76; p < 0.0001) and preoperative radiation therapy (OR, 1.62; 95 percent CI, 1.04 to 2.52; p = 0.03) were significant independent predictors of venous thrombosis.The authors found a significantly higher rate of venous thrombosis with the 1.5-mm-diameter coupler than with larger diameter devices or hand-sewn venous anastomoses. This evidence suggests that surgeons should choose an outflow vessel that does not require a coupler diameter smaller than 2.0 mm or perform a hand-sewn anastomosis in situations where this is not possible.Therapeutic, III.