OBJECTIVE To evaluate the impact of suture caliber and looped configurations on the integrity of 4-strand modified Kessler zone II flexor tendon repairs during progressive cyclic loading. METHODS Seventy-two flexor digitorum profundus tendons from 18 fresh human cadaver hands were divided into 4 repair groups. Thirty-six matched tendons underwent repair using either a 4-0 looped or 4-0 single-stranded suture, and an additional 36 tendons underwent 3-0 looped or 3-0 single-stranded repairs. Repair strength was tested by progressive cyclic loading. The force generating 2-mm gap formation, ultimate failure, and the mechanism of failure were recorded for each test. The impact of looped versus single-stranded configurations and the effect of tendon cross-sectional area on repair integrity were analyzed for each suture caliber. RESULTS There was no statistically significant difference between groups regarding the force to 2-mm gap formation or ultimate failure, and all values exceeded the minimum threshold of 27 N required to withstand an early active range of motion rehabilitation protocol. The use of a 3-0 caliber suture resulted in a significantly higher proportion of repairs failing by suture pullout through the tendon substance, including 63.5% of looped and 38.9% of single-stranded core sutures. By comparison, this occurred in 11.1% of 4-0 looped and 0% of 4-0 single-stranded sutures. Larger tendon cross-sectional areas were associated with more robust repairs, particularly in the 3-0 looped group. CONCLUSIONS In a human cadaver flexor tendon repair model, there was no significant difference in the mean force to failure between all 4 flexor tendon repair constructs under progressive cyclic loading. However, the 3-0 caliber suture failed more frequently by suture pullout, particularly with the use of a looped suture. CONCLUSIONS Four-strand flexor tendon repairs using a 3-0 caliber suture are more prone to early failure by suture pullout under progressive cyclic loading compared with a 4-0 caliber suture.