Purpose: The use of blunt-threaded titanium interference screws for arthroscopic-assisted fixation of a quadruple-strand hamstring anterior cruciate ligament (ACL) reconstruction has recently been reported. However, the pitfalls of the low medial portal technique, rehabilitation protocol, and long-term results have not. The purpose of this multicenter study was to prospectively evaluate this technique's application to ACL instability in symptomatic patients as well as to develop a standardized rehabilitation protocol. Type of Study: Observation cohort study. Methods: One hundred-twenty patients had quadruple hamstring ACL reconstructions, followed the study protocol, and were seen at 2 years follow-up. They were evaluated using Lysholm score, Lachman test, anterior drawer test, pivot-shift test, KT-1000, effusion assessment, and the Tegner Sports Activity Scale. Results: The average Lysholm score improved 42 points; Lachman test, effusion assessment, anterior drawer test, KT-1000, and Tegner Sports Activity Scale scores all improved. Of 120 ACL reconstructions, 5 failed. Of these, 3 failed from new late injury, 1 from technical error, and 1 from patient nonadherence to rehabilitation protocol. Some anterior knee pain was present in 30% of patients, and 22% had at some time experienced hamstring pain that did not interfere with athletic activity. Conclusions: This multicenter study reports success with quadruple hamstring ACL reconstruction using the low medial portal technique. Specific pitfalls and a rehabilitation protocol are also discussed. Low medial portal position is critical in successful surgery. Variations in screw size to accommodate the variation in graft construct size are also recommended.