ABSTRACT Aim To compare the compressive strengths of composite resins and resin-modified glass ionomer cements (RMGICs) at different times. Materials and methods A total of 36 samples were prepared, 12 samples of each group, composite resins Filtek Z 250, Filtek Z 350, and resin-modified glass ionomer cement. Compressive strengths of specimens were measured after 1, 24 hours, and 7 days. Test was carried out on a “Universal Testing Machine” with cross-head speed of 5 mm/min. Results There was a significant difference between all the three restorative materials. Analysis of variance showed that mean compressive strengths of Z 250 after 1, 24 hours were higher than Z 350 and RMGIC (p < 0.05). The mean compressive strengths were reduced after 7 days in all the three groups, but after 7 days, the values of Z 250 when compared with the Z 350 and RMGIC were higher. Conclusion The study demonstrated that compressive strengths of hybrid composite resins (Z 250) were significantly higher than that of nanocomposites (Z 350) and RMGIC. How to cite this article Sharma A, Mishra P, Mishra SK. Time-dependent Variation in Compressive Strengths of Three Posterior Esthetic Restorative Materials: An in vitro Study. Int J Prosthodont Restor Dent 2016;6(3):63-65.