Background: Polycarprolactone and beta tricalcium phosphate (PCL/β-TCP) are resorbable biomaterials that exhibit ideal mechanical properties as well as high affinity for osteogenic cells. Aim: Objective of this study was to evaluate healing and tissue reaction to the PCL/β-TCP barrier membrane in the rabbit calvaria model for guided bone regeneration. Materials and Methods: The PCL/β-TCP membranes were 3D printed. Three circular defects were created in calvaria of 10 rabbits. The three groups were randomly allocated for each specimen: (i) sham control; (ii) PCL/β-TCP membrane (PCL group); and (iii) PCL/β-TCP membrane with synthetic bone graft (PCL-BG group). The animals were euthanized after two (n = 5) and eight weeks (n = 5) for volumetric and histomorphometric analyses. Results: The greatest augmented volume was achieved by the PCL-BG group at both two and eight weeks (p p = 0.04). The PCL/β-TCP membrane remained intact after eight weeks with slight degradation, and showed good tissue integration. Conclusions: PCL/β-TCP membrane exhibited good biocompatibility, slow degradation, and ability to maintain space over eight weeks. The 3D-printed PCL/β-TCP membrane is a promising biomaterial that could be utilized for reconstruction of critical sized defects.