It has been reported that mesenchymal stem cells (MSCs) have homing capacities and immunomodulating effects after an intravenous injection. However, transplanting MSCs in murine tail veins can result in pulmonary reactions and even death of the animals. Unfortunately, only a few intravenous MSC transplantations have been reported in large animal species and these were performed in a limited number of individuals. To assess the safety of MSC transplantations, a large study on 291 recipient horses is reported here. MSCs were isolated from the peripheral blood (PB) of a 4-year-old and 6-year-old donor horse after having tested their PB for a wide range of transmittable diseases. The MSC samples from both donor horses were characterized and resuspended in 1ml of Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% Dimethyl Sulfoxide (DMSO). After hand-thawing in the field, 291 horses with ages ranging from 3-months to 33-years were directly injected into their jugular vein. 281 horses (97%) received a single injection of a physiological dose of 0.2 x106 MSCs, 5 horses (1.7%) were re-injected after approximately 6 weeks (using the same dose and donor cells) and a single superphysiological dose of 106 MSCs was administered to 5 horses as well. In total, 176 recipients were injected with MSCs from the 4-year-old donor and 115 recipients received MSCs from the 6-year-old donor. From all the injected horses (n=291) no acute clinical adverse effects were noticed. Apart from one horse that died of colic 7 months after the treatment, no deaths were registered and all the horses were monitored for 1 year after the injection. In conclusion, no adverse effects were noticed in 291 recipients after an intravenous injection of allogenic PBderived MSCs. Nevertheless, further research is warranted in order to verify the immunogenic properties of these cells after allogenic transplantation into various (patho)physiological sites.