PURPOSE: To compare clinical outcomes of patients undergoing isolated patellofemoral autologous chondrocyte implantation (ACI) and ACI combined with patellofemoral realignment. METHODS: A systematic review was performed by use of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines/checklist. We searched PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), SportDiscus, and the Cochrane Central Register of Controlled Trials databases from 1946 through February 2012 to determine whether a difference exists in outcomes of combined ACI and osteotomy versus isolated ACI (minimum 2 years' follow-up). Studies were included only if outcomes were reported separately for both isolated ACI and combined ACI and osteotomy. All ACI generations were eligible for inclusion. Patellofemoral osteotomies eligible for inclusion were anteriorization, medialization, or anteromedialization. All patient-, limb-, and defect-specific characteristics were assessed. All reported clinical scores, radiographic and histologic outcomes, and complications/reoperations were analyzed. Risk of bias was assessed within all studies. RESULTS: Eleven studies (10 Level III or IV evidence) (366 subjects) were included. Of the defects treated, 78% were located on the patella and 22% on the trochlea. The mean subject age was 33.3 years. Twenty-three percent of subjects underwent concomitant osteotomy. The mean length of follow-up was 4.2 years. Significant (P < .05) improvements in patients undergoing both isolated ACI and combined ACI and osteotomy for patellofemoral chondral defects were observed in all studies. Three studies directly compared isolated ACI and combined ACI and osteotomy, with significantly (P < .05) greater improvements shown in patients undergoing combined osteotomy and ACI (International Knee Documentation Committee subjective score, Lysholm score, Knee Injury and Osteoarthritis Outcome Score, Tegner score, modified Cincinnati score, Short Form 12 score, and Short Form 36 score). There was no significant difference between groups in the rate of postoperative complications overall. CONCLUSIONS: This review showed statistically significant improvements in patients undergoing both isolated ACI and ACI combined with osteotomy for patellofemoral chondral defects in all studies. When individual studies compared these 2 groups (3 studies), significantly greater improvements in multiple clinical outcomes in subjects undergoing ACI combined with osteotomy were observed. There was no significant difference in the rate of total complications between groups. LEVEL OF EVIDENCE: Level IV, systematic review of studies with minimum Level IV evidence, retrospective case series.