The purpose of this study was to determine the minimum number of throws needed for knot security for square knots using 5 common suture materials and 3 common sizes by in vitro single load to failure biomechanical testing. The hypothesis was that each suture combination studied would share a common minimum of at least 5 throws to guarantee security. Five suture materials (FiberWire [Arthrex, Inc, Naples, Florida], Monosof, Surgipro, Maxon, and Polysorb [Covidien, Mansfield, Massachusetts]) with varying suture sizes (#5, #2, 0, 2-0, and 4-0) were tied in vitro, varying the number of square knot throws (3, 4, 5, and 6). Twenty knots for each combination were statically loaded to failure in tension; whether the knot failed by fracture or slippage and the tensile strength at knot failure was determined. For the tested materials, at least 5 flat square throws should be used to confer knot security based on a binomial proportion score 95% confidence interval (CI) 0.84 to 1.0 or at least 4 throws for a 95% CI of 0.76 to 0.99. FiberWire requires 6 flat square throws per knot for security at either 95% CI level. Unless a surgeon has specific knowledge of experimental evidence that fewer throws are necessary for a specific application, the default should be a minimum of 4 throws, with 5 conferring additional security in most situations, and FiberWire requiring 6 throws.