Background and purpose Nabiximols is a therapeutic option for patients with multiple sclerosis (MS) spasticity whose symptoms are poorly controlled by conventional oral first‐line medications. This study aimed to assess the relationship between changes in spasticity severity (measured on the 0–10 numeric rating scale NRS) and the presence of associated symptoms in patients treated with nabiximols, and to investigate the presence of the newly described ‘spasticity‐plus syndrome’. Methods We analyzed real‐world data from the Italian Medicines Agency e‐Registry on 1138 patients with MS spasticity who began treatment with nabiximols. Evaluation time points were baseline, 4 weeks, and 3, 6, 12 and 18 months after treatment start. Results Common symptoms associated with MS spasticity in this cohort were pain (38.4% at baseline), sleep disturbances (32.7%), and spasms/cramps (28.5%). Pain was frequently clustered with sleep disturbances (57.2% of pain cases) and spasms/cramps (43.9%). Approximately one‐third of patients with data at all evaluation time points maintained treatment at 18 months. Nabiximols reduced the baseline mean spasticity 0–10 NRS score by 24.6% at Week 4, and by 33.9% at 18 months in treatment continuers. Nabiximols resolved a range of MS spasticity‐associated symptoms at Week 4, and after 18 months in treatment continuers. Conclusion This real‐world analysis supports the concept of a spasticity‐plus syndrome and suggests that nabiximols can favorably impact a range of spasticity‐associated symptoms. This Agenzia Italiana del Farmaco (Italian Medicines Agency) e‐Registry analysis examined the presence of ‘spasticity‐plus syndrome’ in patients with multiple sclerosis (MS) spasticity treated with nabiximols oromucosal spray (n = 1138). The most common spasticity‐associated symptoms at baseline were pain (38.4%), sleep disturbances (32.7%), and spasms/cramps (28.5%). Spasticity‐associated symptoms were present in fewer patients who were still receiving nabiximols at 18 months and had available symptom data (n = 179). No relevant differences in symptom resolution rates were observed according to MS type, disease duration or gender. Along with relevant and durable improvement in MS spasticity, nabiximols responders can experience resolution of MS spasticity‐associated symptoms.