OBJECTIVE While single-position surgery (SPS) eliminates the need for patient repositioning, the placement of screws in the unconventional lateral position poses unique challenges related to asymmetry relative to the surgical table. Use of robotic guidance or intraoperative navigation can help to overcome this. The aim of this study was to compare the relative accuracies offered by these various navigation modalities for pedicle screws placed in lateral SPS. METHODS According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the PubMed/Medline, Embase, and Cochrane Library databases were queried for studies reporting pedicle screw placement accuracy using fluoroscopic, CT-navigated, O-arm, or robotic guidance in lateral SPS, and a systematic review and meta-analysis was performed. Included studies all compared evaluated screw placement accuracy in lateral SPS using a single navigation method. Quality assessment was performed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system; risk of bias was assessed using the Newcastle-Ottawa Scale and the Joanna Briggs Institute checklist. The primary outcome, rate of pedicle screw breach, was analyzed using random-effects meta-analysis. RESULTS Eleven studies were included comprising 548 patients who underwent the placement of instrumentation with 2488 screws. For the fluoroscopic, CT-navigated, O-arm, and robotic guidance cohorts, there were 3, 2, 3, and 3 studies, respectively. Breach rates by modality were as follows: fluoroscopic guidance (6.6%), CT navigation (4.7%), O-arm (3.9%), and robotic guidance (3.9%). Random-effects meta-analysis showed a significant difference between studies, with an overall breach rate of 4.9% (95% CI 3.1%–7.5%; p < 0.001); however, testing for subgroup differences failed to show a significant difference between guidance modalities (Q_M = 0.69, df = 3; p = 0.88). Heterogeneity between studies was significant (I² = 79.0%, τ² = 0.41, χ² = 47.65, df = 10; p < 0.001). CONCLUSIONS Robotic guidance of screws is noninferior to alternative guidance modalities in lateral SPS; however, additional prospective studies directly comparing different guidance types are merited.