Background: Restoring decayed teeth in young patients can be challenging. This calls for a simplification of the protocols through new biomaterials. Therefore, the aim of this study was to compare the marginal adaptation delivered by restorative materials applied on class II cavities by using a simplified protocol, before and after fatigue test, followed by the assessment of the internal adaptation.

Methods: Forty-eight human teeth were divided into six groups (n = 8). Dentinal fluid simulation was performed before restoring the class II cavities: Gr 1—adhesive (Clearfil Universal Bond Quick) and nanohybrid flowable composite (Clearfil Majesty ES Super Low Flow), Gr 2—adhesive (Clearfil Universal Bond Quick) and nanohybrid composite (Clearfil Majesty ES standard), Gr 3—bulk fill self-adhesive composite (Surefil One), Gr 4—bioactive powder-liquid filling material (Cention Forte), Gr 5—universal adhesive (Adhese Universal) and nanohybrid composite resin (Tetric Powerfill); and control group (CT)—high-viscosity glass ionomer (Equia Forte). Marginal adaptation was observed with scanning electron microscopy (SEM) and compared before and after a fatigue test consisting of repeated thermal and mechanical cycles. The specimens were then cut mesio-distally, and internal adaptation was undertaken using SEM again. Repeated measures and one way ANOVA followed by a Fisher’s LSD test and Fisher’s LSD post hoc test were used in order to compare the statistically significant differences among groups.

Results: As for the marginal adaptation after loading, Cention Forte (58%) and Equia Forte HT (53%) were statistically equivalent and presented the highest results, followed by Clearfil Majesty ES Standard (32%) and Tetric Powerfill (27%), with Surefil One (8%) and Clearfil Majesty ES Flow Super Low (7%) showing the worst results. In terms of internal adaptation, Cention Forte (85%) and Clearfil Majesty ES Standard (74%) had the highest percentages of continuous margins. Tetric powerfill (56%) and Equia Forte HT (44%) showed statistically significantly lower results, followed by Clearfil Majesty ES Flow Super Low (33%) and eventually Surefil One (17%).

Conclusions: This in vitro study showed promising results for the marginal and internal adaptation of alkasite dual cured Cention Forte in the restoration of class II cavities. This material could be considered an interesting restorative alternative for the restoration of deciduous teeth.