Blood clots are pivotal for haemostasis and regeneration¹, but they are mechanically weak and form slowly², posing risks for life-threatening haemorrhage and limiting broader applications^3,4,5. These limitations are attributed to complex coagulation cascades, abundant mechanically ineffective cells and little structural polymers. Strategies that strengthen polymer networks are inapplicable to these highly cellularized materials. Here we report a strategy that rapidly crosslinks red blood cells into tough cytogels and integrates them within blood clots. The resulting engineered blood clots (EBCs) form within seconds and exhibit a 13-fold increase in fracture toughness, and a 4-fold improvement in adhesion energy compared with native clots. Experiments and modelling identify the rupture of mechanically integrated cells as a key toughening mechanism. In vivo studies demonstrate that EBCs can rapidly halt haemorrhage, promote tissue regeneration, mitigate inflammation and foreign body reactions, and prevent postoperative adhesion. The safety and efficacy of both autologous and allogeneic EBCs were also validated. Our strategy is applicable to a range of cells and polymers. This work may motivate the development and translation of highly cellularized materials for bleeding control, wound management, tissue repair and regenerative medicine.