OBJECTIVE:Persistent symptoms and poor quality of life (QoL) are common following anterior cruciate ligament reconstruction (ACLR). We aimed to determine the influence of a combined ACL injury (i.e., concomitant meniscectomy and/or arthroscopic chondral defect at the time of ACLR and/or secondary injury/surgery to ACLR knee) and MRI-defined cartilage defects, bone marrow lesions (BMLs) and meniscal lesions on patient-reported outcomes (PROs) 1- to 5-years post-ACLR METHODS: 80 participants (50 men) aged 32±14 years completed the Knee injury and OA Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) questionnaire, and 3T MRI assessment at 1- and 5-years post-ACLR. Median PRO scores were compared between isolated and combined ACL injuries, and with published normative values. Multivariate regression evaluated the association between compartment-specific MRI cartilage, BMLs and meniscal lesions, and PROs at 1- and 5-years. RESULTS:Individuals with a combined injury had significantly worse KOOS-Sport, and IKDC scores at 1-year, and worse KOOS-Pain, KOOS-Symptoms, KOOS-QoL, and IKDC scores at 5-years, compared to those with an isolated injury. Whilst no feature on MRI was associated with PROs cross-sectionally at 1-year, patellofemoral cartilage defects at 1-year were significantly associated with worse 5-year KOOS-Symptoms (β: -9.79; 95%CI:-16.67, -2.91), KOOS-Sport (β: -7.94; 95%CI:-15.27, -0.61), KOOS-QoL (β: -8.29; 95%CI:-15.28, -1.29) and IKDC (β: -4.79; 95%CI:-9.34, -0.24). Patellofemoral cartilage defects at 5-years were also significantly associated with worse 5-year KOOS-Symptoms (β: -6.86; 95%CI:-13.49, -0.24) and KOOS-QoL (β: -11.71; 95%CI:-19.08, -4.33). CONCLUSION:Combined injury, and patellofemoral cartilage defects on MRI are associated with poorer long-term outcomes. Clinicians should be vigilant to these individuals, who may benefit from targeted interventions to improve QoL and optimise symptoms. This article is protected by copyright. All rights reserved.