The aim of the present in vivo microcomputed tomography (μCT) and histologic experiment was to assess the efficacy of guided bone regeneration (GBR) around standardized calvarial defects using recombinant human platelet-derived growth factor (rhPDGF) with and without resorbable collagen membrane (RCM). A total of 50 female Wistar albino rats with a mean age of 7.5 months and mean weight of 275 g were used. The calvarium was exposed following midsagittal scalp incision and flap reflection. A full-thickness standardized calvarial defect (4.6 mm diameter) was created. Study animals were randomly divided into five groups based on biomaterials used for GBR within the defect: (1) no treatment (negative control), (2) bone graft alone (BG), (3) bone graft covered by RCM (BG + RCM), (4) bone graft soaked in rhPDGF (BG + rhPDGF), and (5) bone graft soaked in rhPDGF and covered with RCM (BG + rhPDGF + RCM). In vivo μCT for determination of newly formed bone volume (NFBV) and mineral density (NFBMD) and remnant bone particles volume (RBPV) and mineral density (RBPMD) was done at baseline and at 2, 4, 6, and 8 weeks postoperatively. Eight weeks following surgery, the animals were sacrificed and harvested calvarial specimens were subjected to histologic and biomechanical analysis. There was an increase in NFBV and NFBMD associated with a corresponding decrease in RBPV and RBPMD in all the study groups. Two-way analysis of variance revealed significant differences in the measured values within and between the groups across the timelines examined during the study period (P < .05). While the NFBV was significantly higher in the bone graft, BG + RCM, and BG + rhPDGF + RCM groups, the NFBMD was similar in all the groups except negative control. The greatest decreases in RBPV and RBPMD were observed in the BG + rhPDGF + RCM group in comparison to the other groups. Similarly, BG + rhPDGF + RCM groups had hardness and elastic modulus similar to that of natural bone. The in vivo μCT results were validated by the qualitative histologic findings. In real time, new bone formation starts as early as 2 weeks in rat calvarial defects treated with bone graft and rhPDGF, irrespective of the presence or absence of RCM.