Abstract Purpose: The purpose of this study was to compare the abrasion resistance of different types of non-absorbable braided sutures under varying in vitro conditions of cyclic loading. Type of Study: Biomechanical study. Methods: Two types of nonabsorbable braided sutures were used in this study, No. 2 Ethibond and No. 2 Fiberwire, combined with 5 different anchors: 5.0-mm Corkscrew anchor, 5.0-mm BioCorkscrew anchor, 3.0-mm BioFastak anchor, Panalok RC anchor, and 3.5-mm Panalok anchor. Twelve tests for each construct were performed. A custom-designed testing apparatus was constructed to evaluate the abrasion resistance of sutures through an anchor eyelet. The apparatus cycled the suture through the anchor eyelet at a rate of 84 revolutions per minute and a speed of 12.5 m/min. In addition to suture type, the effect of different suture-to-anchor angles and testing conditions (dry v wet testing) were evaluated. The number of cycles to failure and the mode of failure were recorded (suture breakage v eyelet breakage). Results: Results showed that under all testing conditions No. 2 Fiberwire displayed abrasion resistance superior to No. 2 Ethibond ( P < .002 in all cases). The mean number of cycles to failure was 5 to 51 times greater when using No. 2 Fiberwire than when using No. 2 Ethibond. Altering the suture-to-anchor angle from 0° (in-line) to 45° decreased the abrasion resistance of both No. 2 Ethibond (69.8 cycles ± 26.5 cycles v 7.4 cycles ± 3.9 cycles; P < .000004) and No. 2 Fiberwire (918.3 cycles ± 417.4 cycles v 389.2 cycles ± 195.7 cycles; P = .001) when using the 5.0-mm Corkscrew anchor. Fiberwire performed equally well under both dry and wet conditions ( P > .05) whereas Ethibond performed better under wet conditions ( P = .0002) when using the 5.0-mm BioCorkscrew anchor. When using the Panalok RC anchor (mean failure, 11.2 cycles ± 1.3 cycles) or the 3.5-mm Panalok anchor (mean failure, 12.5 cycles ± 2.4 cycles), constructs failed at significantly lower cycles than other comparable anchor-suture constructs ( P < .00007 in all cases). In addition, although the vast majority of failure modes for the other anchor-suture constructs was by suture breakage, the Panalok RC anchor and 3.5-mm Panalok anchor consistently failed by cutting of the suture through the biodegradable eyelet. Conclusions: (1) Suture abrasion differs according to the suture type, anchor type, and testing conditions. (2) No. 2 Fiberwire showed superior resistance to abrasion when compared with No. 2 Ethibond under all conditions tested in the study. (3) The abrasion resistance of No. 2 Fiberwire is sufficiently high to eliminate, clinically, the theoretical concerns over weakening of suture from the anchor eyelet. (4) Suture eyelets formed of biodegradable materials can fail at low numbers of cycles by cutting of the suture through the biodegradable eyelet during cyclic loading. Clinical Relevance: The study will help the surgeon to assess suture and suture anchor characteristics in order to optimize fixation of biologic tissues during surgical repair and reconstruction.