Introduction: There is lack of consensus regarding best operative fixation strategy for periprosthetic femoral fractures (PFFs) around a stable stem. Evidence exists that some patterns of fracture around a stable stem are better treated with revision surgery than with standard fixation. Anyway, a more aggressive surgical procedure together with medical treatment could allow for stem retention, and reduced risk of nonunion/hardware failure, even in these cases., Significance: This paper is placed in a broader context of lack of studies on the matter, and its aim is to shed some light on the management of PFFs around a stable stem, when peculiar mechanical and biological aspects are present., Results: Based on our casuistry in the treatment of nonunions after PFF successfully treated with original stem retention, and on review of Literature about risk factors for fixation failure, an algorithm is proposed that can guide in choosing the ideal surgical technique even for first-time PFFs with a stable stem, without resorting to revision. Mechanical (major and minor) and biological (local and systemic) factors that may influence fracture healing, leading to nonunion and hardware failure, and subsequent need for re-operation, are considered. The proposed surgical technique consists of rigid fixation with absolute stability (using a plate and structural allograft) plus local biological support (structural allograft and autologous bone marrow concentrate over a platelet-rich plasma-based scaffold) at fracture site. Systemic anabolic treatment (Teriparatide) is also administered in the post-operative period., Conclusion: Mechanical factors are not the only issues to be considered when choosing the surgical approach to PFFs over a stable stem. Systemic and local biological conditions should be taken into account, as well. A therapeutic algorithm is proposed, given the prosthetic stem to be stable, considering mechanical and biological criteria., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)