Purpose: Multiple preparation protocols for platelet-rich fibrin (PRF) are in use today, and clinical results are often heterogeneous. This study analyzes the impact of the chosen PRF preparation protocol on 1) wound healing and 2) alveolar ridge preservation. Methods: For this systematic review and meta-analysis, eligible studies were identified in PubMed and Cochrane databases. Included were randomized controlled and controlled clinical trials with healthy patients treated with PRF after atraumatic tooth extraction compared to untreated socket(s), reporting at least one of the following outcome variables: pain, swelling, soft tissue healing, alveolar osteitis risk, horizontal and vertical bone loss, socket fill, and new bone formation. Main predictor variable was relative centrifugal force (RCF) comparing high RCF (high PRF), intermediate RCF (standard [S-PRF]), low RCF (advanced PRF), and various RCF settings (concentrated growth factor preparation [CGF]). The type of centrifugation tubes (silica-coated plastic and glass) was a secondary predictor. Weighted or standardized mean differences, risk ratio and corresponding 95% confidence intervals were calculated. Results: Forty studies published between 2012 and 2022 were selected. The pooled effects of all outcomes were significant against untreated sockets. Within the subgroups high PRF or advanced PRF had the lowest efficacy for many outcome parameters. Pain reduction (in visual analog scale units) was highest for S-PRF (−1.18 [−1.48, −0.88], P <.00001) and CGF (−1.03 [−1.16, −0.90], P <.001). The risk ratio of alveolar osteitis (0.09 [0.01, 0.69], P <.02) and soft tissue healing (standardized mean difference = 2.55 [2.06, 3.03], P <.001) were best for CGF. No subgroup differences were found for bone-related outcomes. No meaningful analysis of the tube material effect was possible. Conclusion: This study confirms that PRF is associated with reduced postoperative complications but indicates that preparation protocol influences clinical outcomes. S-PRF and CGF protocols appear to be superior for several outcome parameters.