Positive effects of platelet-rich fibrin (PRF) on soft tissue healing are well documented, but its role in hard-tissue healing remains contested. The present case series documents the use of PRF as the sole grafting material in periapical bone defects. PRF was prepared and condensed into the bone defects after debridement. The defects were then covered with a collagen membrane and wound closure was performed. In all three cases presented in this report, excellent bone fill was observed in the periapical defects. The observed benefit may be due to the role of fibrin in initial clot stabilization. The elaboration of various growth factors by the platelets and leukocytes in the PRF clot may also play a role.