OBJECTIVE To compare the immediate microtensile bond strengths (µTBSs) of four mild self-etch universal adhesives applied to dentin and enamel with self-etch and etch-and-rinse techniques. METHODS Flat middle dentin surfaces from 104 human teeth and two enamel fragments from another 104 human teeth were randomly distributed into eight groups according to the various adhesive systems used: Scotchbond Universal (SBU) [etch-and-rinse mode vs. self-etch mode]; Optibond XTR (OPT) [ etch-and-rinse mode vs. self-etch mode]; Clearfil Universal Bond Quick (CL) [ etch-and-rinse mode vs. self-etch mode]; and Adhese Universal (ADH) [etch-and-rinse mode vs. self-etch mode]. After 24 hours of water storage, the bonded sticks were tested for µTBS. The differences in the pre-test failure and fracture-failure modes were tested by a two-way ANOVA and GEE model analysis. Bond-strength data were analyzed with a two-way ANOVA and mixed-model analysis. RESULTS : For dentin, the mean µTBS was statistically different among the four adhesives, but not different between the self-etch and etch-and-rinse modes. For enamel, the mean µTBS was statistically different among the four adhesives, as was the application mode. GEE model analysis revealed a statistically significant adhesive failure rate proportion among the four types of adhesives for both enamel and dentin. CONCLUSIONS Etching enamel prior to the application of a universal adhesive can be recommended as an approach to enhance bond strength.