The purpose of this study was to investigate the tensile strength of the bond between a silicone lining material and heat-cured polymethyl methacrylate (PMMA) denture base resin after Er:YAG laser treatment with different pulse durations and energy levels. PMMA test specimens were fabricated and each received one of six surface treatments: no treatment (control), and five Er:YAG laser treatments comprising (1) 100 mJ, 1 W, long pulse duration, (2) 200 mJ, 2 W, long pulse duration, (3) 200 mJ, 2 W, very short pulse duration, (4) 300 mJ, 3 W, long pulse duration, and (5) 400 mJ, 4 W, long pulse duration. The resilient liner specimens (n = 15) were processed between two PMMA blocks. The tensile strengths of the bonds between the liners and PMMA were determined using a universal testing machine at a crosshead speed of 5 mm/min. The mode of failure was characterized as cohesive, adhesive, or mixed modes. One-way ANOVA and the post hoc Tukey-Kramer multiple comparisons test were used to analyze the data (alpha = 0.05). There was a statistically significantly difference in tensile bond strength between laser-treated and untreated specimens (P < 0.05). The 300-mJ, 3 W, long pulse duration laser treatment produced the highest mean tensile bond strength. In addition, the long pulse duration treatments resulted in greater bond strength than very short pulse duration treatment (P < 0.05). Laser irradiation produced significant surface texture changes of the denture base material and improved the adhesion between denture base and soft lining material. In addition, different pulse durations and energy levels were found to effectively increase the strength of the bond.