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To perform a systematic review of clinical outcomes following microfracture augmented with biological adjuvants (MFX+) compared with microfracture (MFX) alone.The MEDLINE, Scopus, and Cochrane databases were searched for clinical studies on MFX+ for chondral defects of the knee. Study characteristics and clinical outcome score data were collected. Subjective synthesis was performed using data from randomized controlled studies to determine effect size of MFX+ procedures performed with either injectable or scaffold-based augmentation compared with MFX alone.A total of 18 articles reporting on 625 patients (491 MFX+, 134 MFX) were identified. Six studies were level II evidence and 1 study was level I evidence. Mean patient age range was 26 to 51 years, and mean follow-up ranged from 2 to 5 years. All studies demonstrated significant improvement in reported clinical outcome scores at follow-up after MFX+ therapy, and 87% of patients reported satisfaction with treatment. The most commonly reported treatment complication was postoperative stiffness (3.9% of patients). Subjective synthesis on randomized controlled trials demonstrated that 2/2 injectable MFX+ interventions had significantly greater improvements in International Knee Documentation Committee Subjective Knee Form (IKDC; P = 0.004) and Knee injury and Osteoarthritis Outcome Score (KOOS; P = 0.012) scores compared with MFX alone, while 2/2 trials on scaffolding MFX+ adjuvants showed comparable postoperative improvements.MFX+ biological adjuvants are safe supplements to marrow stimulation for treating cartilage defects in the adult knee. Early literature is heterogenous and extremely limited in quality. Individual trials report both equivalent and superior clinical outcomes compared with MFX alone, making definitive conclusions on the efficacy of MFX+ difficult without higher quality evidence.