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The aim was to investigate the influence of endodontic irrigation solutions and protocols on the micro-tensile bond strength (μTBS) to dentin using an etch-and-rinse (ER) or self-etch (SE) adhesive approach. Eighty extracted human molars were ground to dentin. After pretreating for 27 min (21 min–3 min–3 min) with five different endodontic irrigation protocols (Group 1: NaOCl–EDTA–NaOCl; Group 2: NaOCl–NaOCl–EDTA; Group 3: NaOCl–NaCl–NaOCl; Group 4: Dual Rinse–Dual Rinse–Dual Rinse; Group 5: NaCl–NaCl–NaCl), an ER (Optibond FL, Kerr) or a SE (Clearfil SE Bond, Kuraray) adhesive system was applied. After light-curing, composite build-ups were made and cut into dentin-composite sticks. μTBS and failure modes were analyzed. Nonparametric statistical analyses (α = 0.05) were performed for comparison of the five groups within each type of adhesive as well as between the two adhesive systems used. The use of an ER instead of a SE adhesive system resulted in significantly higher μTBS for all irrigation protocols except for group 1 (NaOCl–EDTA–NaOCl) and 2 (NaOCl–NaOCl–EDTA). A statistical difference between the five different endodontic irrigation protocols was only found within the SE adhesive group, where group 1 (NaOCl–EDTA–NaOCl) achieved highest values. The use of an ER adhesive system cancels out the effect of the endodontic irrigation solution. The highest μTBS was achieved when using a NaOCl–EDTA–NaOCl-irrigation protocol in combination with Clearfil SE Bond, which shows that the selection of the endodontic irrigation should match the corresponding SE adhesive system. [ABSTRACT FROM AUTHOR]