PurposeTo investigate patient demographic, injury and surgery/treatment‐associated factors that can influence the patient‐reported outcome (Lysholm score), following autologous chondrocyte implantation (ACI) in a large, ‘real‐world’, nonuniform, prospective data examined retrospectively.MethodsKnee patients treated at the Robert Jones and Agnes Hunt Orthopaedic Hospital, UK, using ACI between 1996 and 2020 were eligible. All longitudinal postoperative Lysholm scores collected between 1 and 23 years after ACI treatment and before any second major procedure (e.g., arthroplasty) were included. Multilevel longitudinal models were built investigating the association of short‐term (1 year) or long‐term trends in Lysholm score with baseline demographic, clinical and cell‐culture variables, namely age, gender, smoker status, body mass index, baseline Lysholm score, time from surgery, defect grade, diameter and location, number of defects, previous microfracture, patch/scaffold type, associated procedure(s), number of cells implanted and their passage number.ResultsFollowing filtering, 306 of the 427 knee ACI procedures reviewed were suitable for inclusion. Factors shown to result in higher postoperative Lysholm scores in the short term were lower patient age, higher baseline Lysholm scores, fewer implanted cells and a lateral femoral defect location. The factor which was associated with higher long‐term postoperative Lysholm scores was a milder defect grade. Additionally, the failure rate in this cohort was explored and it was found that 73/306 (24%) of patients experienced joint failure according to our definition. Furthermore, the outcome was not influenced by coincidental procedures in this cohort of patients.ConclusionsThis study has identified a number of baseline factors associated with patient‐reported outcomes following ACI and shows that treatment of associated pathology at the time of surgery potentially restores patient outcomes to a similar level as those with no associated pathologies.Level of EvidenceLevel IV.