Background: Following primary chemoradiotherapy for squamous cell carcinoma of the anal canal (A-SCCa), 10% of patients have persistent cancer, and 30% develop local recurrence after initial complete response. Both persistent and recurrent A-SCCa may be amenable to salvage surgery, which typically involves intense health care resource utilization. Because only small cohorts have been reported, we synthesized the evidence for salvage surgery to gain a comprehensive understanding of outcomes. Methods: We systematically searched MEDLINE, Embase, and Cochrane Library (until October 11, 2018) for studies reporting on persistent or recurrent A-SCCa treated with salvage surgery. Quality assessment was performed using the Institute of Health Economics Quality Appraisal Checklist. Overall survival (OS) and disease-free survival (DFS) were pooled using two approaches: survival curve meta-analysis, and exact binomial likelihood random-effects model for survival probabilities. We used meta-regression, subgroup and sensitivity meta-analyses to explore sources of heterogeneity. Results: We identified 39 observational studies that included 1388 patients. Pooled 5-year OS was 45.5% (95% CI 40.6 to 49.9; 33 studies; 1308 patients), and did not differ in patients resected for recurrent (14 studies, n=259 patients) vs. persistent (n=238 patients) disease. There was no association of OS with study year, tumor size, or resection margin at the aggregate-level. Pooled 5-year DFS was 38.3% (95% CI 31.4-43.9; 14 studies; 554 patients). Pooled 30-day complications were 65.3% (95% CI 50.2-77.9; 17 studies; 720 patients): major complications 27.7% (95% CI 22.3-33.8), reoperations 12.7% (95% CI 8.7-18.2), and mortality 1.7% (95% CI 1.1-2.6%). Pooled perineal complications were 32.7% (95% CI 25.0-41.4). Conclusions: Salvage surgery offers 5-year OS of ≈45% and DFS of ≈40% for recurrent/persistent A-SCCa. Major complications and perineal wound complications are common, but postoperative mortality is rare. Presently, there are no reports of patient-reported outcomes such as quality of life after salvage surgery for A-SCCa. Comparative effectiveness studies comparing surgery to other treatments are warranted.