We found that (i) platelets modulate specific endothelial functions relevant for angiogenesis through C5aR1, (ii) platelet C5aR1 mediates an inhibitory effect on collateral artery formation in ischemia-induced revascularization and (iii) capillary formation and pericyte coverage, (iv) platelets release CXCL4 upon C5a stimulation, and (v) the platelet C5aR1-mediated effect on vessel formation is mediated by preferential CXCL4 release in vitro and in vivo. Here, C5 is linked to ischemia.