Context. Patients with post-stroke spasticity (PSS) commonly experience pain in affected limbs, which may impact quality of life. Objectives. To assess onabotulinumtoxinA for pain in patients with PSS from the BOTOX (R) Economic Spasticity Trial, a multicenter, randomized, double-blind, placebo-controlled trial. Methods. Patients with PSS (N = 273) were randomized to 22- to 34-week double-blind treatment with onabotulinumtoxinA + standard care (SC) or placebo injection + SC and were eligible to receive open-label onabotulinumtoxinA up to 52 weeks. Assessments included change from baseline on the 11-point pain numeric rating scale, proportion of patients with baseline pain amp;gt;= 4 achieving amp;gt;= 30% and amp;gt;= 50% improvement in pain, and pain interference with work at Week 12, end of double-blind treatment, and Week 52. Results. At baseline, most patients (74.3%) experienced pain and 47.4% had pain amp;gt;= 4 (pain subgroup). Mean pain reduction from baseline at Week 12 was significantly greater with onabotulinumtoxinA + SC (-0.77, 95% CI -1.14 to -0.40) than placebo + SC (-0.13, 95% CI -0.51 to 0.24; P amp;lt; 0.05). Higher proportions of patients in the pain subgroup achieved amp;gt;= 30% and amp;gt;= 50% reductions in pain at Week 12 with onabotulinumtoxinA + SC (53.7% and 37.0%, respectively) compared with placebo (28.8% and 18.6%, respectively; P amp;lt; 0.05). Reductions in pain were sustained through Week 52. Compared with placebo + SC, onabotulinumtoxinA consistently reduced pain interference with work. Conclusion. This is the first randomized, placebo-controlled trial demonstrating statistically significant and clinically meaningful reductions in pain and pain interference with work with onabotulinumtoxinA in patients with PSS. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine. This is an open access article under the CC BY-NC-ND license.