Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by episodic yet cumulative heterotopic ossification (HO), which develops connections to the normal skeleton, resulting in progressive immobility. The heterotopic bone cannot be resected because such procedures result in regrowth of the resected lesions and induction or exacerbation of additional HO. FOP is caused by mutations in ACVR1, with the most common mutation altering arginine 206 to histidine ( ACVR1R206H). Using a genetically accurate mouse model of FOP – 129;B6N-Acvr1tm2Vlcg (aka Acvr1[R206H]FlEx)/+ Gt(ROSA26)Sortm3.1(cre/ERT2)Vlcg/+ – we have demonstrated that unlike wild type ACVR1, ACVR1R206H perceives activin A as an agonistic ligand, and that it is this new property of ACVR1R206H that drives HO. Furthermore, using neutralizing anti-activin A antibodies we have shown that there is an absolute requirement for activin A to initiate HO (Hatsell, Idone et al; PMID 26333933). Here we extend our findings and demonstrate that inhibition of activin A in a delayed dosing setting (where the mice are allowed to form HO over three weeks and then dosing with the antibody is initiated), as well as in a surgery setting (where an HO lesion is resected while the mice are administered antibody) provides ‘therapeutic’ benefit. In both settings, inhibition of activin A stops further growth of existing or partially resected HO lesions. Importantly, whereas surgery (in the absence of anti-activin A) induces ‘explosive’ growth of the resected lesion as well as nearby lesions, this effect is greatly inhibited in the presence of the antibody. Given that the majority of FOP patients already present with ongoing or existing HO at the time of diagnosis (and also the number of patients with developed disease), our results not only demonstrate that activin A remains a key HO-promoting factor even after initiation of HO but also indicate a new potential path to therapy, and indeed one where surgical intervention may be incorporated.