Purpose To investigate the effect of various surface pretreatments and adhesive systems on bond strength of resin cement to polyetheretherketone (PEEK). Materials and Methods 360 PEEK specimens were divided into 4 groups to receive the following pretreatments (n = 90): no pretreatment, sandblasting, silica coating and Er:YAG laser. Surface roughness (SR) and scanning electron microscopy (SEM) evaluations were conducted after mechanical pretreatments for topographical surface evaluations. After the pretreatments, each group was divided into 3 subgroups (n = 30) according to the adhesive system used: no adhesive system, Visio.link, and Signum PEEK Bond. Resin cement was applied, and specimens underwent 5000 thermocycles (5-55 degrees C) before shear bond strength (SBS) test. One-way ANOVA and Tukey test were used to analyze the SR data; 2-way ANOVA and Fisher's LSD test were used to analyze the SBS data at the confidence interval of 95% (alpha = 0.05). Results The sandblasting group demonstrated the highest SR values (p < 0.05). No significant differences in SR values were identified among silica coating, laser, and control groups (p > 0.05). Conditioning with Visio.link after sandblasting group exhibited the highest SBS values (p < 0.05). No significant differences in SBS values were found between laser and control group (p > 0.05). Conditioned groups presented higher SBS values than unconditioned groups (p < 0.05). Between the two adhesive systems, Visio.link demonstrated statistically significant higher SBS values than Signum PEEK Bond (p < 0.05). Conclusion Silica coating and sandblasting were shown to provide superior pretreatment of PEEK surface. Laser pretreatments showed no effectiveness on bond strength of resin cement to PEEK. Adhesive systems improved the resin bonding to PEEK.