In order to enable various etching modes and enhance bond strength, MM adhesives contain functional monomers in their formulation, such as Phenyl-P (N-Phenyl-p-phenylenediamine), 4-MET (4-methacryloxymethyl trimellitic acid) or MDP (methacryloyloxi-decyl-dihydrogen-phosphate). These monomers interact chemically with hydroxyapatite, producing self-assembled nano-layers. The intensity of the process depends on the type of monomer and MDP has proved to be the most efficient one [18]. A nano-layered structure is strongly hydrophobic and helps to protect the formed hybrid layer against hydrolysis [18; 19], therefore positively influencing bond strength to dentin. Other constituents of MM adhesives, which may enhance adhesion to tooth structures, are biphenyl dimethacrylate (BPDM), dipentaerythnitol pentaacrylate phosphoric acid ester (PENTA) and polyalkenoic acid copolymer [6]. Also, a combination of hydrophilic (hydroxyethul methacrylate, HEMA), hydrophobic (decandiol dimethacrylatelite, D3 MA) and intermediate (bisphenol A-glycidyl methacrylate, bis-GMA) monomers have been employed in the composition of MM adhesives [6]. The hydrophilic ends of these monomers interact with dentin, while the hydrophobic ends interact with methacrylate-based restorative materials or cross-link with other monomers. In case of amphiphilic MDP, its terminal ends are hydrophilic initially but become more hydrophobic when they react chemically with tooth tissues and are polymerized [17]. Also, additives to MM adhesive composition, such as silane, potentially eliminate the silanization step when placing direct or indirect restorations made of glass ceramics, zirconia, metal or resin composites, defining the universal clinical indications of such adhesives [6; 20]. In the same time, one should bear in mind that the composition of MM adhesives, aimed at the simplification of the clinical procedure and improvement of bond strength, not only results in their antibacterial activity, e.g., against _S. mutans_[21], but is also inseparably linked with cytotoxicity, e.g., on gingival fibroblasts [22]. According to recent studies, the application of SE and MM adhesives in SEE mode is the most effective protocol to ensure a durable bond to dental tissues [3; 23]. When bonding to etched enamel, these adhesives obtain satisfactory results [24]. Yet, when bonding to dentin, alterations of the application procedure were suggested in order to further improve the bond strength of both SE and MM adhesives [25]. These alterations included extending the application time [26] and multiplying the number of consecutive applications (no light-curing in between) [27] or layers (each layer light-cured) [27]. The aim of this study was to determine the effect of multiple applications and extended application time of self-etch and universal adhesives on dentin bond strength and on thickness of adhesive layer as well as the correlation between these parameters. The null hypotheses tested are: (1) There is no effect of multiple applications and extended application time of self-etch and universal adhesives on dentin bond strength. (2) There is no effect of multiple applications and extended application time of self-etch and universal adhesives on thickness of adhesive layer. (3) There is no correlation between adhesive layer thickness and dentin bond strength.