Purpose This study investigated the long-term effect of Er:YAG laser pretreatment on the adhesion of a self-etch adhesive system to caries-affected dentin (CAD). Methods Ninety human dentin specimens were submitted to Streptococcus mutans biofilm cariogenic challenge (7 days) to obtain artificial CAD lesions (4 × 5 mm). Groups were defined by the surface pretreatment [no pretreatment; 80 mJ, 2 Hz, 50 μs, Results Three-way ANOVA and Tukey's multiple comparison tests (α = 0.05) showed that CAD had lower μSBS values than SD after 1 year despite surface pretreatments (p = 0.00). AL nanohardness test revealed that specimens' hardness decreased after 1 year (p = 0.00). The HL produced had lower nanohardness in CAD than in SD, which decreased over time for all surface pretreatments (p = 0.00). SEM analysis revealed that all adhesive interfaces, especially in CAD, degraded after 1 year. Conclusions Caries-affected dentin did not seem to be an adequate substrate for bonding. Er:YAG laser irradiation did not influence adhesion to CAD and SD.