Despite the molecular and histological similarities between fetal bone development and fracture healing, inflammation is an early phase of fracture healing that does not occur during development. Cyclo‐oxygenase 2 (COX‐2) is induced at inflammation sites and produces proinflammatory prostaglandins. To determine if COX‐2 functions in fracture healing, rats were treated with COX‐2‐selective nonsteroidal anti‐inflammatory drugs (NSAIDs) to stop COX‐2‐dependent prostaglandin production. Radiographic, histological, and mechanical testing determined that fracture healing failed in rats treated with COX‐2‐selective NSAIDs (celecoxib and rofecoxib). Normal fracture healing also failed in mice homozygous for a null mutation in the COX‐2 gene. This shows that COX‐2 activity is necessary for normal fracture healing and confirms that the effects of COX‐2‐selective NSAIDs on fracture healing is caused by inhibition of COX‐2 activity and not from a drug side effect. Histological observations suggest that COX‐2 is required for normal endochondral ossification during fracture healing. Because mice lacking Cox2 form normal skeletons, our observations indicate that fetal bone development and fracture healing are different and that COX‐2 function is specifically essential for fracture healing.