Background: Unicompartmental tibiofemoral bipolar osteochondral allograft transplantation (OCAT) with meniscal allograft transplantation (MAT) has not historically been associated with consistently successful outcomes for treatment of knee articular cartilage defects with meniscal deficiency. Hypothesis: Primary OCAT and MAT using fresh tissues will be associated with successful short-term outcomes based on statistically significant and clinically meaningful improvements in pain and function in the majority of patients. Study Design: Case series; Level of evidence, 4. Methods: Patients were prospectively enrolled into a registry for outcomes after OCAT and MAT. Patients included those who underwent primary OCAT and MAT using Missouri Osteochondral Preservation System (MOPS)–preserved allografts for treatment of large bipolar tibiofemoral articular cartilage defects with meniscal deficiency and had a minimum of 2-year follow-up data. Results: A total of 76 patients (n = 52 male; 68%) met inclusion criteria (mean follow-up, 52 months). The mean age was 41.1 years (range, 15-69 years), and the mean body mass index was 28.9 (range, 17-46); 48 patients underwent another OCAT in addition to the unicompartmental bipolar tibiofemoral OCAT and MAT; 23 patients (30.3%) were documented to be nonadherent to the prescribed postoperative restriction and rehabilitation protocol. The initial success rate (>2 years) was 77.6%, with 8 patients (10.5%) undergoing revision and 9 (11.8%) converting to arthroplasty. Variables associated with an increased risk for treatment failure (revision or arthroplasty) included ipsilateral osteotomy (P = .046; odds ratio [OR] = 3.3), ipsilateral concurrent procedure (P = .0057; OR = 5.5), and nonadherence (P = .0009; OR = 7.2). None of the patients undergoing revision surgery required arthroplasty at the time of data analysis such that the overall success rate for primary and revision unicompartmental bipolar OCA plus MAT was 88.2%. There were statistically significant (P < .0001) and clinically important improvements for all patient-reported outcomes at each annual follow-up time point. Conclusion: Unicompartmental tibiofemoral bipolar OCAT and MAT can result in successful short-term outcomes (2-6 years) and satisfaction in the majority of patients (78%). Primary MOPS-preserved OCAT with MAT for treatment of femoral condyle and tibial plateau articular cartilage defects with concurrent meniscal deficiency was associated with statistically significant and clinically meaningful improvements in patient-reported measures of pain and function.