OBJECTIVE: Based on recent success of intra-articular (IA) Botulinum neurotoxin type A (BoNT/A; OnabotulinumtoxinA) in patients with osteoarthritis, we examined if repeat IA-BoNT/A is an effective antinociceptive in patients with refractory arthroplasty pain. METHODS: 11 patients with refractory chronic arthroplasty joint pain without any evidence of infection or prosthesis loosening were referred by orthopedic surgeons. After discussion of off-label use, each patient underwent IA injection of BoNT/A, repeated based on return of pain on numeric rating scale (NRS) and functional limitation on composite validated scales, Western Ontario McMaster Osteoarthritis index (WOMAC) or Shoulder Pain and Disability (SPADI). RESULTS: 11 patients (10 men, 1 woman) with 14 painful arthroplasty joints (3 bilateral; 12 knee and 2 shoulder) underwent ≥1 IA-BoNT/A injections (8 joints injected once, one joint injected twice only, five joints injected thrice) with doses ranging 100-300 units. Mean age was 68 years (standard deviation, 12) and follow-up ranged 1-28 months. Clinically meaningful reduction of 2-units in pain severity and really meaningful reduction in pain severity (50% reduction) were reported by 6/11 patients (6/13 joints) and 3/11 patients (3/13 joints), respectively, 1 month after the first IA-BoNT/A (100-units each). Significant improvements were noted in composite functional scales (WOMAC/SPADI). Pain relief was sustained at 3-4 month follow-up and was reproducible in those who received repeat injections. No significant adverse events were seen in any patients. CONCLUSIONS: A single intra-articular injection of BoNT/A improved pain and function in patients with chronic, refractory painful knee or shoulder arthroplasty, which sustained with repeat injections. Patients who were refractory to the first injection, did not respond to subsequent injections of higher dose of IA-BoNT/A.