Pain reduction is a common goal of the treatment of upper limb spasticity with botulinum toxin (BoNT-A). ULIS-III was a large international, observational, longitudinal study (N = 953) conducted in real-life clinical practice over two years. In this secondary post hoc analysis, we examine whether goals for pain reduction were met over repeated injection cycles. We report serial changes in pain severity and explore predictors of pain reduction and injection frequency. Patients were selected if pain reduction was a primary/secondary goal for at least one cycle (n = 438/953). They were assessed at the start and end of each cycle using the goal attainment T-score alongside a self-report of pain severity (range 0-10). Across all cycles, pain-related goals were set for 1189/1838 injections (64.7%) and were achieved in 839 (70.6%). Patients continued to show a significant reduction in pain (