Bone mineral density (BMD) loss is one of the secondary problems occurring in knee joint after injury of anterior cruciate ligament (ACL). The effect of this injury on BMDs of specific regions is not clear. The aim of this study was to investigate BMD changes in unreconstructed ACL-deficient knees with subregion analysis of dual energy X-ray absorptiometry (DEXA). Precision and reliability studies of DEXA revealed that two region of interests (ROI) in medial condyle, two ROIs in lateral femoral condyle (LFC) and one ROI in medial tibial plateau (MTP) in anteroposterior (AP) DXA view and one ROI for each of distal femur, proximal tibia and patella in lateral view had high reproducibility and reliability. Thirty-two patients with complete ACL ruptures were collected for the study and uninjured sides served as the control. All the patients were male with a mean age of 30 years. Mean duration of ACL rupture was 24 months. There were significant BMD losses in both ROIs of LFC and ROI of MTP in AP view and all three ROIs of lateral view. Greatest BMD losses in AP and lateral views were at MTP and patella respectively. There was a significant association between patellar BMD loss and duration after trauma. Bone bruises in lateral condyle might be the cause of selective involvement of LFC. Periarticular bone mineral loss in ACL-deficient knees has a predilection for the specified region of interest rather than uniform periarticular loss. This may be important for graft fixation or a factor in tunnel enlargement.