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Abstract: Background: The use of bioactive proteins, such as rhBMP‐2, may improve bone regeneration in oral and maxillofacial surgery. Purpose: Analyze the effect of using bioactive proteins for bone regeneration in implant‐based rehabilitation. Materials and Methods: Seven databases were screened. Only clinical trials that evaluated the use of heterologous sources of bioactive proteins for bone formation prior to implant‐based rehabilitation were included. Statistical analyses were carried out using a random‐effects model by comparing the standardized mean difference between groups for bone formation, and risk ratio for implant survival (P ≤ .05). Results: Seventeen studies were included in the qualitative analysis, and 16 in the meta‐analysis. For sinus floor augmentation, bone grafts showed higher amounts of residual bone graft particles than bioactive treatments (P ≤ .05). While for alveolar ridge augmentation bioactive treatments showed a higher level of bone formation than control groups (P ≤ .05). At 3 years of follow‐up, no statistically significant differences were observed for implant survival (P > .05). Conclusions: Bioactive proteins may improve bone formation in alveolar ridge augmentation, and reduce residual bone grafts in sinus floor augmentation. Further studies are needed to evaluate the long‐term effect of using bioactive treatments for implant‐based rehabilitation. [ABSTRACT FROM AUTHOR]