The transtibial (TT) drilling of the femoral tunnel in the bone-patellar tendon-bone (BPTB) anterior cruciate ligament (ACL) reconstruction was found to place the tunnel non-anatomically. The use of the anteromedial portal (AMP) for the femoral drilling would provide the surgeon with more freedom to anatomically place the tunnel in the real femoral ACL footprint. The purpose of this study was to compare the clinical outcomes of BPTB ACL reconstruction using the AMP or the TT technique for the femoral tunnel drilling. A Medline search was not able to identify any study directly comparing the clinical outcomes of the AMP and the TT techniques. The literature search identified experimental and quasi-experimental studies published from 1966 to March 2009 where at least one group underwent arthroscopic autologous BPTB ACL reconstructions using either the AMP or the TT technique for the femoral tunnel drilling. Overall IKDC, Lysholm score, activity level, range of motion, single-leg hoop test, Lachman test, Pivot shift sign test, KT-1000 arthrometer measurements, and radiographic assessments were indirectly compared between the two groups (AMP versus TT). Twenty-one studies, involving a total of 859 patients (257 in the AMP and 602 in the TT group), were included in this analysis. The AMP group demonstrated significantly earlier return to run and significantly greater range of motion, Lachman test values, and KT-1000 arthrometer measurements in the 1-2-year follow-up, although no differences were found for both the 3-5 and the 6-10-year follow-ups for any of these parameters. In contrast, the TT group demonstrated significantly higher activity level for the 3-5 and 6-10-year follow-up. The use of the AMP elicited greater knee stability and range of motion values, and earlier return to run compared to the TT technique. These results may indicate a potential benefit of the AMP over the TT technique. However, as the benefits of the AMP were not obtained in the mid and long-term follow-ups, overall there is no definitive evidence at this point to conclude that one technique is superior to the other. Randomized controlled trials directly comparing the use of both techniques with long-term follow-ups will help clarify which one, if any, provides best clinical outcomes.