Antegrade reamed intramedullary nailing has the advantages of high fracture union and early weight-bearing, making it the gold standard for fixation of diaphyseal femur fractures. However, knowledge of distal femoral anatomy may mitigate the risk of secondary complications. We present a previously unrecognized complication of antegrade femoral nailing in which a 23-year-old man sustained iatrogenic rupture of the medial patellofemoral ligament (MPFL) caused by the distal interlocking screw of the femoral nail. The patient had a history of antegrade intramedullary nailing that was revised for rotational malalignment, after which he began experiencing recurrent episodes of atraumatic bloody joint effusion and swelling of the right knee with associated patellar instability. Plain radiographs and magnetic resonance imaging revealed a large effusion with a prominent intra-articular distal interlocking screw disrupting the MPFL. The patient underwent a right knee arthroscopic-assisted MPFL reconstruction and removal of the distal interlocking screw. Following surgery, the patient experienced resolution of his effusions, no recurrent patellar instability, and was able to return to his activities. This case demonstrates that iatrogenic MPFL injury is a potential complication of antegrade femoral nailing and a previously unrecognized cause of patellar instability. Surgeons should be aware of this potential complication and strive to avoid the MPFL origin when placing their distal interlocking screw.