Retrograde drilling is an established surgical technique to treat osteochondral lesions of the talus (OLT). It involves non-trans-articular drilling to induce subchondral bone revascularization and bone formation without damaging the overlying articular cartilage. The present study aimed to elucidate the heterogeneity of clinical studies on retrograde drilling for OLT. A systematic search of the MEDLINE, Web of Science, EMBASE, and Cochrane Library databases for studies published between January 1996 and August 27, 2022, was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by two independent reviewers. The included studies were evaluated for their level of evidence (LoE) and quality of evidence (QoE) using the Modified Coleman Methodology Score. Variables reporting surgical and clinical outcomes and complications were evaluated. Eleven studies with 207 ankles were included (mean follow-up period = 31.1 months). The mean LoE was 3.8 (LoE 3: two studies, LoE 4: nine studies), and the mean QoE was 50.8 (fair: three studies, poor: eight studies). Ten studies used the American Orthopedic Foot and Ankle Society (AOFAS) score, which improved from 57.9 preoperatively to 86.1 postoperatively. The period and protocol of conservative treatment, lesion character, surgical technique, and postoperative protocol were inconsistent or underreported. This systematic review revealed that low LoE and poor QoE, coupled with heterogeneity among the included studies, impede definitive conclusions regarding the effectiveness of this technique. Consequently, well-designed clinical trials are essential to develop standardized clinical guidelines for using retrograde drilling in OLT.