There is little information about the management of peri-prosthetic fracture of the humerus after total shoulder replacement (TSR). This is a retrospective review of 22 patients who underwent a revision of their original shoulder replacement for peri-prosthetic fracture of the humerus with bone loss and/or loose components. There were 20 women and two men with a mean age of 75 years (61 to 90) and a mean follow-up 42 months (12 to 91): 16 of these had undergone a previous revision TSR. Of the 22 patients, 12 were treated with a long-stemmed humeral component that bypassed the fracture. All their fractures united after a mean of 27 weeks (13 to 94). Eight patients underwent resection of the proximal humerus with endoprosthetic replacement to the level of the fracture. Two patients were managed with a clam-shell prosthesis that retained the original components. The mean Oxford shoulder score (OSS) of the original TSRs before peri-prosthetic fracture was 33 (14 to 48). The mean OSS after revision for fracture was 25 (9 to 31). Kaplan-Meier survival using re-intervention for any reason as the endpoint was 91% (95% confidence interval (CI) 68 to 98) and 60% (95% CI 30 to 80) at one and five years, respectively. There were two revisions for dislocation of the humeral head, one open reduction for modular humeral component dissociation, one internal fixation for nonunion, one trimming of a prominent screw and one re-cementation for aseptic loosening complicated by infection, ultimately requiring excision arthroplasty. Two patients sustained nerve palsies. Revision TSR after a peri-prosthetic humeral fracture associated with bone loss and/or loose components is a salvage procedure that can provide a stable platform for elbow and hand function. Good rates of union can be achieved using a stem that bypasses the fracture. There is a high rate of complications and function is not as good as with the original replacement.