Study design: Randomized clinical trial. Objectives: To investigate the immediate effects of soft tissue mobilization (STM) versus therapeutic ultrasound (US) in patients with neck and arm pain who demonstrate neural mechanical sensitivity. Background: While experts have suggested that individuals with neck and arm pain associated with neural tissue mechanical sensitivity may benefit from STM, there has been little research to investigate this hypothesis. Methods: Twenty-three patients with neck and arm pain and a positive upper limb neurodynamic test (ULNT) were randomly assigned to receive STM or therapeutic US during a single session. Outcome measures were collected immediately before and after treatment, and at 2-4 day follow-up. Primary outcomes were the Global Rating of Change (GROC), range of motion (ROM) during the ULNT, and pain rating during the ULNT. Secondary measures included the Neck Disability Index (NDI), Patient-Specific Functional Scale (PSFS), Numeric Pain Rating Scale (NPRS), and active range of shoulder abduction motion combined with the wrist neutral or wrist extension. Results: A greater proportion of patients in the STM group reported a significant improvement on the GROC immediately after treatment (P50.003, STM575%, US59%), and at 2-4 day follow-up (P50.027, STM558%, US59%). Patients who received STM demonstrated greater improvements in ROM during ULNT (P50.026), PSFS (P50.007), and shoulder active ROM combined with wrist extension (P50.028). Improvements in Numeric Pain Rating Scale and pain during the ULNT were observed only in the STM group. There was no difference between groups for the NDI or shoulder abduction ROM with wrist neutral. Conclusion: Patients with neck and arm pain demonstrated greater improvements in ULNT ROM, GROC, and PSFS, and pain following STM than after receiving therapeutic US. Level of evidence: Therapy, level 1b.