Purpose: This study systematically reviewed the literature to compare the bonding ability of dental adhesives applied to sound dentin (SoD) vs caries-affected dentin (CAD). Materials and Methods: Three international databases (Medline/PubMed, Scopus, and Web of Science) were searched. Eligible studies which evaluated the bond strength to both SoD and CAD were included. Random effects meta-analyses were conducted to calculate pooled mean difference between substrates, separately for etch-and-rinse and self-etch adhesives. Subgroup analyses were carried out to explore heterogeneity considering the methods used for removal of infected carious dentin. A comparison between etch-and-rinse and self-etch adhesives restricted to CAD was also performed. Statistical heterogeneity was considered using the I2 test. The risk of bias of all included studies was assessed. Results: In total, 2260 articles were found, 65 were selected for full-text reading, and 40 studies were included. The meta-analyses favored SoD over CAD for both etch-and-rinse (effect size: -10.04; 95% confidence interval [CI]: -11.94, -8.14; I2 = 95%) and self-etch adhesives (effect size: -6.76; 95% CI: -8.23, -5.30; I2 = 89%). In the subgroup analyses, SoD was favored irrespective of the method used for caries removal (effect size ≤ -4.86; I2 ≥ 28%): excavation (manual or with burs), grinding with abrasive papers, combination of more than one method, and when the method was not mentioned. The meta-analysis restricted to CAD favored etch-and-rinse over self-etch adhesives (effect size: 3.13; 95% CI: 1.82, 4.44; I2 = 72%). Most included studies were judged as having an unclear risk of bias. Conclusion: Bonding to SoD yields better results compared to CAD. Etch-and-rinse adhesives performed better than self-etch adhesives when applied to CAD. Schlagwörter: adhesion, caries detection, dental tissues, etch-and-rinse adhesives, resin-based restoratives, self-etch adhesives