Mohamed Abdel-MonemTawfik ^a, EmanAbd El-Salam Yousef ^b,MahitabeFathyElgamily ^c , Ibrahim Abdel-MonemElboghdadi ^d. ^aProfessor  and Chairman of Oral and Maxillofacial Surgery Department, Faculty of Dentistry, Mansoura University, Mansoura, Egypt. ^bLecturer of Oral Surgery Department, Faculty of Dentistry, Mansoura University, Mansoura, Egypt. ^cLecturer of Oral Biology Department, Faculty of Dentistry, Mansoura University, Mansoura, Egypt. ^dMaster Degree of Oral and Maxillofacial surgery, Faculty of Dentistry, Mansoura University, Egypt. Abstract: Background: Over the past decade, use of platelet rich fibrin (PRF) has gained tremendous momentum in regenerative dentistry as a low cost fibrin matrix used for tissue regeneration and improving the healing process. Aim of the study: This study was designed to evaluate the effect of PRF versus Advanced PRF on bone healing experimentally and on soft tissues healing clinically. Materials and Methods: Experimental part; Normal 30 adult male guinea pigs weighing between (400-500 gm) with 4 mm bilateral cortical bony defects prepared in the submental area.Then divided into 2 groups, 15 animals each. The right bone defects of group (I) were filled with PRF clot,  also the right bone defects of group (II) were filled with  A-PRF. In both groups the left bony defects were left empty. All animals  in both groups were euthanized at 15, 30, and 45 days of follow up for further histological assessment. Clinical part; 36 patients with an average age of 26 years seeking surgical extraction of 36 mandibular impacted third molars and met the inclusion criteria were included. All patients were equally and randomly divided into 3 groups;  A, B and C. Each group consisted of 12 teeth. After tooth extraction,  A-PRF clot was placed in group (A), PRF was placed in group (B), while no material was placed in group (C). The evaluated criteria were pain, analgesic consumption, soft tissue healing and socket complications encountered during the first postoperative week. All data collected were analyzed using SPSS version 20.0 software. Statistical significance was inferred at a P value ≤ 0.05. Results: Histological results;   A high significant difference was recorded between groups regarding to amount of bone formation at different periods of follow up either  at 15, 30, and 45 days (P ≤ 0.001). Clinical results. Regarding the severity of pain and analgesic consumption, no statistical significant differences were found between group (A) and (B) values recorded at the  second (p < sub>1=0.508,p < sub>1=0.894 ), third (p < sub>1=0.922, p < sub>1=0.152), fourth (p < sub>1=0.625, p < sub>1=0.218), fifth (p < sub>1=0.624, p < sub>1=0.214), sixth (p < sub>1=0.830, p < sub>1=0.440) and seventh (p < sub>1=0.930, p < sub>1=0.808) post-operative days respectively. Clear significant differences were found between group (A) and (C) values recorded at the second (p < sub>2=0.010, p < sub>2=0.028), third (p < sub>2=0.004,p < sub>2=0.001), fourth (p < sub>2=0.009, p < sub>2=0.002),  fifth (p < sub>2=0.004, p < sub>2=0.001),  sixth (p < sub>2=0.007,p < sub>2=0.004) and seventh (p < sub>2=0.006, p < sub>2=0.015) post-operative days respectively. Also a significant differences were found between group (B) and (C) values recorded at third (p < sub>3=0.006, p < sub>3=0.043), fifth (p < sub>3=0.016, p < sub>3=0.049), sixth (p < sub>3=0.013, p < sub>3=0.036) and seventh (p < sub>3=0.004, p < sub>3=0.028) post-operative days respectively. The study showed that there was a statistically significant difference in the degree of soft tissue healing  and socket complications after seven days of extraction among patients in group (A) and group (C) (MCp < sub>2=0.005, MCp < sub>2=0.020) respectively,   but there was no statistically significant difference between patients in group (A) and (B) (MCp < sub>1= 0.621, MCp < sub>1=1.000) and also group (B) and (C) (MCp < sub>3=0.213, MCp3=0.055) respectively. Conclusion:   It can be concluded  that A-PRF enhances soft tissue healing and bone regeneration. Also, it is an effective preventive method that reduces postoperative pain and localized osteitis. On the other hand, PRF has insignificant effect on socket complications and soft tissue healing. .