Developing bio-absorbable interference screws for anterior cruciate ligament (ACL) reconstruction has proven to be a challenging task. The aim of this study was to investigate the osteogenetic response of poly-lactide carbonate (PLC) interference screws in ACL reconstruction in humans. Ten patients (median age, 28 years) underwent arthroscopic ACL reconstruction with semitendinosus/gracilis tendon graft and a PLC interference screw. The patients were scanned with a multi-slice CT scanner 2 weeks and 1 year postoperatively. Fourteen days postoperatively a mean tunnel widening of 78% [52%; 110%] was observed. At 1-year follow-up, the mean tunnel widening was 128% [84%; 180%]. No sign of bone replacement or bone ingrowth was observed. Factors such as accelerated rehabilitation, micro-motions, and early screw degradation might be responsible for this large tunnel widening. Our results demonstrate the difficulty in translation of preclinical data. This study illustrates the need for extensive preclinical investigation of new materials for clinical purposes.