The aim of this study was to evaluate the shear bond strengths (SBSs) of one-step self-etch adhesives containing different co-solvents to enamel and dentin and to determine the failure modes of tested specimens. Two hundred and forty (n = 240) sound human molars were used. The buccal surfaces of each tooth were ground and polished to obtain flat enamel surfaces (n = 120) or to expose the underlying dentin (n = 120). The specimens with exposed enamel or dentin were randomly divided into four main groups (n = 30) according to the one-step self-etch adhesives used: Bond-1 SF, OptiBond All-In-One, G-aenial, and Single Bond Universal adhesive. All the main groups were then subdivided into two subgroups (control and thermocycling subgroups) (n = 15). After bonding procedures, a composite restoration (Filtek Z250) was applied in a vinyl tube and condensed against the cured adhesive bonding agent, to form a resin cylinder. The specimens were stored in distilled water at 37°C for 24 hours (control and thermocycling subgroups), followed by thermocycling (5-55°C/5,000 cycles + storage in artificial saliva for 2 weeks) (thermocycling subgroup). They were subjected to SBS testing in a universal testing machine at a crosshead speed of 0.5 mm/minute. After being shear-tested, all fractured samples were examined by means of a Hirox Digital Microscope at 50× magnification for failure analysis. The data were analyzed by one-way analysis of variance followed by Tukey's post hoc analysis at a p value of ≤0.05. OptiBond All-In-One adhesive showed significantly higher mean SBS values on both types of tooth structures (enamel and dentin) and under different conditions (control and thermocycled) compared with the other three adhesives (p < 0.001), except in the enamel-thermocycled group, where the Single Bond Universal adhesive showed higher mean SBS but without a significant difference compared with the OptiBond All-In-One adhesive (p = 0.266), and there was no significant difference between OptiBond All-In-One and G-aenial Bond in the same group (p = 0.192). Conversely, Bond-1 SF showed significantly lower mean SBS values compared with those of the other three adhesives on different types of tooth structures and under different conditions (control and thermocycled) (p < 0.001). One-step self-etch adhesives containing ethanol as a solvent or co-solvent showed higher SBS compared with the other self-etching bonding agents. The bond strength values of these adhesives to dentin are significantly higher than those to enamel. The types of solvents of one-step self-etch adhesives had an effect on SBS, and the absence of solvent in those adhesives would adversely influence their performance. How to cite this article: Ageel FA, Alqahtani MQ. Effects of the Contents of Various Solvents in One-step Self-etch Adhesives on Shear Bond Strengths to Enamel and Dentin. J Contemp Dent Pract 2019;20(11):1260-1268.