Objective: To assess the safety profile of onabotulinumtoxinA for treatment of upper limb spasticity (ULS) across a range of doses, including doses 400U. Design: Post-hoc assessment of integrated data from 18 completed studies (11 double-blind, placebo-controlled and 7 open-label studies) of onabotulinumtoxinA for ULS across 4 dose groups: <150U, 150-250U, 251-399U, and 400U. Setting: Neurology and rehabilitation clinics. Participants: Subjects included adult patients who received 1 treatment of onabotulinumtoxinA for ULS; 51 patients received 4 consecutive treatments of 400U with a variable treatment interval, and 44 received 4 consecutive treatments of 400U administered at 10-14 week intervals. Interventions: Subjects were treated with protocol-specific or physician-determined doses of onabotulinumtoxinA. Main Outcome Measures: Treatment exposure, incidence of adverse events (AEs) and serious AEs, and the potential distant spread of toxin (PDSOT) were assessed, along with the safety profile of patients who received 4 consecutive treatments of onabotulinumtoxinA 400U. Results or Clinical Course: At least 1 onabotulinumtoxinA treatment was received by 1342 patients. Overall, 183 patients received a dose of 400U, with 6.6% (88/1330), 12.3% (115/936), 23.3% (113/486), and 31.2% (96/308) receiving 400U in treatment cycles 1-4, respectively. Across the 4 dose groups (<150U, 150-250U, 251-399U, and 400U) AE rates were similar, with no consistent increase in the incidence of any individual AE or serious AE, and no evidence of PDSOT at doses 400U across treatment cycles. The overall AE rate among the subset of patients (n¼51) with 4 consecutive 400U treatments with a variable treatment interval was similar (43. 1%, 43.1%, 43.1%, 41.2% at treatment cycles 1-4, respectively). There was no overall change in profile for AEs or serious AEs with increasing treatments. Conclusions: OnabotulinumtoxinA at doses 400U was well tolerated in ULS patients, with no consistent pattern of increase in AEs, reported systemic AEs, or change in safety profile over consecutive treatments at doses 400U.