The life situation of many patients changes after an anterior cruciate ligament (ACL) rupture and subsequent reconstruction, and this may affect their health-related quality of life in many ways. It is well known that the overall clinical results after ACL reconstruction are considered good, but pre-operative predictive factors for a good post-operative clinical outcome after ACL reconstruction have not been studied in as much detail. The purpose of this study was to identify pre-operative factors that predict a good post-operative outcome as measured by the Short Form 36 (SF-36) and Knee Osteoarthritis Outcome Score (KOOS) 3–6 years after ACL reconstruction. Seventy-three patients scheduled for ACL reconstruction were clinically examined pre-operatively. The SF-36 and KOOS questionnaires were sent by mail to these patients 3–6 years after reconstruction. Predictive factors for health-related quality of life were investigated using a stepwise regression analysis. In conclusion, pre-operative factors, such as pivot shift, knee function, and range of motion, may predict a good post-operative outcome and explain up to 25% in terms of health-related quality of life after ACL reconstruction. Furthermore, it appears that the patients’ pre-injury and pre-operative Tegner activity levels are important predictors of post-operative health-related quality of life.