Objective: To evaluate the effect of occlusal cyclic loading on the cuspal deflection and adaptation of standardized mesio-occlusal-distal (M.O.D) cavities restored with two different resin composite systems. Methods: A total of 240 freshly extracted, sound, human upper premolars teeth, from an age of 20-40 years extracted for orthodontic purposes were used in the study. A standardized mesio-occlusal-distal (MOD) slot cavity with parallel walls and without proximal step was prepared using a straight diamond fissure bur. Teeth were randomly divided into two equal groups (n= 120) according to type of resin composite used to restore the cavities (R). The combination of Adaper single bond 2/ Filtek Z350XT (Nanofilled, 3M ESPG dental product(USA)) resin composite was used for restoring cavities in the first group (R1), while cavities in the second group (R2) were restored with P90 system adhesive/ Filtek P90 combination (Low shrinkage resin composite, 3M ESPG dental product(USA)). Each group was further subdivided randomly into two equal sub-groups (60 each) according with or without occlusal loading (L). The intercuspal distances of all teeth were measured immediately after cavity preparation (baseline) then after resin composite application (secondary reading), after one month and after 3 months. Adaptation was assessed by examination of linear dye penetration at tooth/ restoration interface at the gingival margins. Results: Low shrinkage resin composite (P90) showed a significant decrease in the cuspal deflection values when compared to nanofilled (Z350 XT) resin composite. Load application produced a significant increase on cuspal deflection for nanofilled resin composite, however low shrinkage (P90) showed that, load application produced an insignificant increase on the cuspal deflection. Cuspal deflection values were not affected by time within the tested groups. Load application increased the micoleakage score for the low shrinkage composite. Conclusion: Low shrinkage resin composite has a significant effect in reduction of the cuspal deflection degree. Adaptation of the low shrinkage composite was adversely affected by load application.