Essentials We examined platelet survival in models of absent or enhanced thrombopoietin (TPO) signaling. Platelet lifespan is normal in transgenic mice with chronically enhanced TPO signaling. Mpl deficiency does not negatively affect platelet lifespan in the absence of thrombocytopenia. We conclude that TPO and its receptor Mpl are dispensable for platelet survival in adult mice.Background It is well established that thrombopoietin (TPO), acting via its receptor Mpl, is the major cytokine regulator of platelet biogenesis. The primary mechanism by which TPO signaling stimulates thrombopoiesis is via stimulation of Mpl-expressing hematopoietic progenitors; Mpl on megakaryocytes and platelets acts to control the amount of TPO available. TPO could potentially reduce platelet and/or megakaryocyte apoptosis, and therefore increase the platelet count. However, the effect of TPO receptor signaling on platelet survival is unresolved. Methods and results Here, we investigated platelet survival in mouse models of absent or enhanced TPO signaling. In the absence of thrombocytopenia, Mpl deficiency did not negatively influence platelet lifespan, and nor was platelet survival affected in transgenic mice with chronically increased TPO signaling. Conclusions We conclude that TPO and its receptor Mpl are dispensable for platelet survival in adult mice.