BACKGROUND Postextraction alveolar bone loss, mostly affecting the buccal plate, occurs despite regenerative procedures. To better understand possible determinants, this prospective case series assesses gingival blood perfusion and tissue molecular responses in relation to postextraction regenerative outcomes. METHODS Adults scheduled to receive bone grafting in maxillary, non-molar, single-tooth extraction sites were recruited. Clinical documentation included the following: 1) probing depth (PD); 2) keratinized tissue width (KT); 3) tissue biotype (TB); and 4) plaque level. Wound closure was clinically evaluated. Gingival blood perfusion was measured by laser Doppler flowmetry (LDF). Wound fluid (WF) and gingival biopsies were analyzed for protein levels and gene expression, respectively, of relevant molecular markers. Bone healing outcomes were determined radiographically (cone-beam computed tomography). Healing was followed for 4 months. RESULTS Data from 15 patients are reported. Postoperatively, neither complications nor changes in PD, KT, or TB were observed. LDF revealed decreased perfusion followed by hyperemia that persisted for 1 month (P ≤0.05). WF levels of angiopoietin-2, interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor peaked on day 6 (P ≤0.05) and decreased thereafter. Only IL-8 and TNF-α exhibited increased gene expression. Linear bone changes were negligible. Volumetric bone changes were minimal but statistically significant, with more bone loss when membrane was used (P = 0.05). CONCLUSIONS Gingival blood perfusion after postextraction bone regenerative procedures follows an ischemia-reperfusion model. Transient increases in angiogenic factor levels and prolonged hyperemia characterize the soft tissue response. These soft tissue responses do not determine radiographic bone changes.