Objective: This study aimed to investigate the efficacy of myofascial release therapy (MRT) for improving pressure pain thresholds (PPTs) and pain in patients with mechanical neck pain. Design: Forty-one participants with neck pain were randomly allocated to either a MRT group (five sessions) or a physical therapy (PT) group (ten sessions) for 2 wks. The multimodal PT program included ultrasound therapy (US), transcutaneous electric nerve stimulation, and massage. Visual analog scale (VAS) and PPTs in suboccipital and upper trapezius muscles were measured at baseline, at the end of treatment, and at 1 month follow-up. Results: At the end of treatment, significant mean differences in VAS (-0.99, 95% confidence interval [CI] = -1.82 to -0.16), in both left (0.28, 95% CI = 0.06 to 0.50) and right (0.40, 95% CI = 0.16 to 0.63) suboccipital PPTs and in the right trapezius PPT (0.38, 95% CI = 0.07 to 0.69) were observed. At 1-month follow-up, significant mean differences were found for VAS (-1.85, 95% CI = -2.76 to -0.94) and both left (0.46, 95% CI = 0.12 to 0.80) and right (0.38, 95% CI = 0.06 to 0.69) suboccipital PPTs. Conclusions: This study provides evidence that MRT could be better than a multimodal PT program for short-term improvement of pain and PPTs in patients with neck pain.