Indiana University-Purdue University Indianapolis (IUPUI) / While most sealants available are resin-based, glass ionomer-based cements can be used as sealants, with the advantage of being more tolerant to moisture during placement and of releasing fluoride. The objective of this study was to evaluate the influence of different fissure conditioning techniques on penetration and microleakage of glass ionomer (GI) and resin-modified glass ionomer cements (RMGI) used as sealants. Clinically sound extracted human molars were distributed into nine experimental groups (n = 15 each). Group 1 (control) was sealed with resin-based sealant (Delton) following clinically accepted techniques. Groups 2 through 6 were sealed with RMGI (Vitremer) after having the fissure conditioned with either polyacrylic acid (RMGI-control), 35-percent H3PO4, low viscosity 35-percent H3PO4 with a surfactant, self-etch conditioner, or 35-percent H3PO4 followed by self-etch conditioner. Groups 7 through 9 were sealed with GI sealant (Fuji Triage) after having the fissures conditioned with either polyacrylic acid (GI-control), 35- percent H3PO4 or low viscosity 35-percent H3PO4 with a surfactant. After aging through thermocycling (2500 cycles), specimens were incubated in methylene blue for four hours and sectioned at multiple locations. Digital images were obtained using a digital stereomicroscope, and microleakage was determined by scoring the dye penetration along the enamel-sealant interface. The penetration of the material was determined by calculating the percentage of the total length of the fissure penetrated by the material. Results: The use of self etch-conditioner significantly increased RMGI penetration, while surface conditioning with 35-percent phosphoric acid with surfactant significantly decreased microleakage of GI. The resin-based sealant placed after 35-percent phosphoric acid surface conditioning showed the best penetration and the least level of microleakage. In conclusion, results from this study suggest that the placement of glass ionomer-based sealants can be enhanced by modifying current conditioning methods.