The aim of this prospective, randomized clinical study was to compare the effectiveness of two physical therapy treatment approaches for impingement syndrome, either by joint and soft tissue mobilization techniques or by a self-training program. Thirty patients (Group 1, n = 15; Group 2, n = 15) with the diagnosis of an outlet impingement syndrome of the shoulder were treated either by strengthening the depressors of the humeral head with a guided self-training program (Group 1, age 49.5 ± 7.9 years), or by joint and soft tissue mobilization techniques (Group 2, age 48.1 ± 7.5 years). Group 1 was instructed with the active range of motion (ROM), stretching and strengthening exercise program including rotator cuff muscles, rhomboids, levator scapulae and serratus anterior with an elastic band at home at least seven times a week for 10–15 min and Group 2 received a prescription for 12 sessions of joint and soft tissue mobilization techniques, ice application, stretching and strengthening exercise programs and patient education in clinic for three times per week. All patients were tested with visual analog scale (VAS) for pain level, goniometric measurement for ROM and algometry for the pain threshold. Function was measured with a functional assessment questionnaire. The VAS (10 cm) used to measure pain with functional activities and the functional assessment questionnaire (Neer) were also measured 3 months after the initiation of treatment. Subjects in both groups experienced significant decreases in pain and increases in shoulder function, but there was significantly more improvement in the manual therapy group compared to the exercise group. For example, pain in the manual therapy group was reduced from a pre-treatment mean (±SD) of 6.7 (±0.3) to a post-treatment mean of 2.0 (±2.0). In contrast, pain in the exercise group was reduced from a pre-treatment mean of 6.6 (±1.4) to a post-treatment mean of 3.0 (±1.8). ROM at flexion, abduction and external rotation in the manual therapy group improved significantly while ROM in the exercise group did not. There were statistically differences among the groups in function (P > 0.05). Group 2 showed significantly greater improvements in the Neer Questionnaire score and shoulder satisfaction score than Group 1. The patients treated with manual physical therapy applied by experienced physical therapists combined with supervised exercise in a brief clinical trial showed improvement of symptoms including increasing strength, decreasing pain and improving function earlier than with exercise program.