Objectives: The purpose of the present study was to review and evaluate the effectiveness of bone substitute materials used for maxillary sinus floor elevation and to propose the most effective bone graft material by assessing newly formed bone, remaining graft particles, and soft tissue ratio. Method and materials: The search protocol used the electronic MEDLINE (PubMed) database for articles published between 1 January 2008 and 1 January 2019. The search was limited to English language only and included clinical studies on humans. Outcomes were the percentage of newly formed bone, remaining graft particles, and soft tissue. Results: Eighteen studies fulfilled the inclusion criteria. Autologous bone and mineralized cancellous bone allograft showed the best results regarding the percentage of newly formed bone (41.74% and 35.41%, respectively). The worst bone formation was observed when Bio-Oss material was used alone (8.25%) and in combination with recombinant human bone morphogenetic protein-7 (rhBMP-7) (6.55%). During estimation of bone regeneration results when anorganic bovine bone (ABB) substitute was used alone and in combination with platelet-rich plasma (PRP), histomorphometric analysis revealed a higher amount of newly formed bone in sites treated with PRP + ABB (31%) compared to ABB alone (21.3%). Conclusions: The present systemic review demonstrated that autologous bone has the best regenerative potential for sinus floor elevation. Combining autologous bone with bone substitutes leads to more matured newly formed bone and better bone graft osseointegration. PRP/plasma rich in growth factors (PRGF) combined together with bone graft materials enhances bone formation and vascularization. It might also reduce inflammation and decrease the risk of complications. Keywords: bone regeneration, bone substitute, histology, sinus floor elevation