Objective: To investigate the effect of low-level laser therapy (LLLT) combined with exercise on shoulder pain and disability in patients with subacromial impingement syndrome (SIS). Design: Randomised controlled trial. Setting: Pontifical Catholic University. Subjects: We enrolled 120 subacromial impingement syndrome patients Intervention: Groups I ( n = 42), II ( n = 42) and III ( n = 36) were treated with Low-level laser therapy and exercise, exercise only and Low-level laser therapy only, respectively. Interventions were conducted three times a week for 8 weeks. Main outcome measures: The primary outcome was the change in shoulder pain and disability index (SPADI). Secondary outcomes included changes in the numeric pain rating scale and medication intake. Results: Average ages of patients in groups I, II and III were 51.9 ± 8.7 years, 56.0 ± 10.4 years and 54.2 ± 7.1 years, respectively. Pain scores at baseline ( P = 0.829), 2 months ( P = 0.057) and 3 months follow-ups ( p = 0.004) were 6.8 (4.7–7.7), 0.2 (0.0–0.5) and 0.3 (0.0–1.0) for group I; 6.6 (5.7–8.0), 0.5 (0.2–2.0) and 0.2 (0.0–3.3) for group II; and 6.5 (5.1–7.4), 2.4 (0.1–6.7) and 4.0 (2.0–5.0) for group III, respectively. SPADI scores at baseline ( P = 0.029), 2 months ( P < 0.001) and 3 months follow-ups ( P = 0.001) were 60.8 (37.7–70.8), 3.8 (0.0–10.8) and 2.3 (0.8–10.8) for group I; 61.5 (41.5–71.5), 9.2 (3.8–29.2) and 14.2 (1.5–38.0) for the group II; and 73.3 (59.2–80.8), 34.2 (16.9–54.6) and 33.1 (22.3–49.2) for the group III, respectively. Conclusion: Low-level laser therapy combined with exercises reduce pain intensity, improve shoulder function and reduces pain intensity and medication intake over 3 months. Clinical Trial Registration number: NCT 02725749