Background: Infiltration and sealing are micro-invasive treatments for arresting proximal non-cavitated caries lesions; however, their efficacies under different conditions remain unknown. This systematic review and meta-analysis aimed to evaluate the caries-arresting effectiveness of infiltration and sealing and to further analyse their efficacies across different dentition types and caries risk levels.Methods: Electronic databases (Cochrane Library, PubMed and Embase) were searched for published literature, and references were manually searched. Split-mouth randomized controlled trials (RCTs) to compare the effectiveness between infiltration/sealing and non-invasive treatments in proximal lesions were included. The primary outcome was obtained from radiographical readings. In total, 995 citations were identified, and 16 RCTs (21 articles) were included.Results: For subgroup analysis, infiltration and sealing reduced the odds of lesion progression (infiltration vs non-invasive: OR = 0.20, 95% CI: 0.15 to 0.29; sealing vs placebo: OR = 0.27, 95% CI: 0.18 to 0.41). For both primary and permanent dentitions, infiltration and sealing were more effective than non-invasive treatments (primary dentition: OR = 0.30, 95% CI: 0.20 to 0.45; permanent dentition: OR = 0.19, 95% CI: 0.13 to 0.27). The overall effects of infiltration and sealing were significantly different from the control effects based on different caries risk levels (OR = 0.19, 95% CI: 0.14 to 0.27). For patients with different risk levels, there were significant differences between micro-invasive and non-invasive treatments (low risk: OR = 0.23, 95% CI: 0.07 to 0.75; low to moderate risk: OR=0.38, 95% CI: 0.18 to 0.81; moderate to high risk: OR=0.17, 95% CI: 0.17 to 0.29; and high risk: OR=0.14, 95% CI: 0.07 to 0.26). Infiltration was superior to non-invasive treatments for patients at different caries risk levels (low risk: OR = 0.07, 95% CI: 0.02 to 0.22; low to moderate risk: OR=0.38, 95% CI: 0.18 to 0.81; moderate to high risk: OR=0.19, 95% CI: 0.09 to 0.38; and high risk: OR=0.14, 95% CI: 0.07 to 0.29).Conclusion: Infiltration and sealing were more efficacious than non-invasive treatments for halting non-cavitated proximal lesions.