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Aim This study evaluated the simultaneous effect of extended etching time and casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) containing paste application on shear bond strength (SBS) of etch-and-rinse adhesive to cariesaffected- dentin (CAD). Materials and methods Fifty human third molars were used; 10 normal in group 1 and 40 caries-affected teeth in groups 2 to 5. In the CAD groups, teeth were randomly assigned into four groups (n = 10). In groups 2 and 4, phosphoric acid etching for 15 and 45 seconds was used and in groups 3 and 5, after 15 or 45 seconds etching respectively, CPP-ACP containing paste (MI paste) was applied for 3 minutes. After rinsing, single bond adhesive system and Z250 composite were used for resin composite build-up in all groups. After storage, SBS test was measured at cross head speed of 0.5 mm/min. Data were analyzed using one/two-way ANOVA and Tukey HSD test (α = 0.05). Results Normal dentin groups showed the highest SBS among different groups. There was a statistically significant difference between different etching times in CAD groups (p < 0.05), but there were no significant differences between SBS of SB adhesive to CAD with or without CPP-ACP pretreated in both etching times. Most of the failure modes were adhesive except in groups 1 and 5 which cohesive failure in composite was also observed. Conclusion The results of our study indicated that extended etching time up to 45 seconds could enhance the SBS of CAD and approach nearly to SBS of normal dentin. Moreover, MI paste pretreatment had not significant effect on SBS of etchand- rinse adhesive in CAD. Clinical significance Simultaneous application of extended etching time and CPP-ACP containing paste may be a suggested method in increasing the SBS of adhesive to CAD. How to cite this article Doozandeh M, Firouzmandi M, Mirmohammadi M. The Simultaneous Effect of Extended Etching Time and Casein Phosphopeptide-Amorphous Calcium Phosphate containing Paste Application on Shear Bond Strength of Etch-and-rinse Adhesive to Caries-affected Dentin. J Contemp Dent Pract 2015;16(10):794-799.