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• This study helps to predict the strength of premolar teeth. • Taguchi Method was used to design the experiments and reduce the number of tests. • The interaction effect results of Taguchi analysis recommended spherical indenter. • The results of SEM indicated that the presence of micro-cracks leads to fracture. • The quality, gender and indenter factors are more effective than other parameters. The purpose of this study is to investigate dental strength and mechanical behavior of Premolar teeth with fissure sealants. Due to the large number of studied parameters, Taguchi algorithm was used to design the experiments and reduce the number of tests. 36 Premolar teeth were selected from three different age groups (child/young/Adult), gender (Male/Female), indenter (Flat/Wedge/Sphere) two types of quality (Intact/Restored) and jaw (Maxilla/Mandible). In this study, two kinds of adhesive (Margin/Single Bond) and fissure sealant material (Seal.it/Wetbond) with various strength and modulus of elasticity were chosen. Also, tooth was stored under different relative humidity amounts (52% and 95%), and was curried by light cure device with intensities of 1000 and 1200 W/cm2. The etching process was performed in acid concentrations of 32% and 37%. The compressive loading was carried out using a universal test machine under displacement-control. The results of interaction effects of gender on age demonstrated that in young age group, male teeth are stronger than female teeth while in child and adult age groups, male and female teeth show relatively same values. The interaction effect results of Taguchi analysis between different indenter surfaces and age groups recommended the spherical indenter, due to the distinction of strength results among different age groups and consequently, ability to investigate the interaction effects between indenter and other parameters. As expected, the results show that the quality factor is the most effective factor. In terms of dental materials and jaw type, the amount of changes is also quite noticeable. Also, the effect of other parameters (humidity, etching, light cure intensity, and adhesive) is negligible in comparison with others. [ABSTRACT FROM AUTHOR]