Background: There are currently many treatment options for patients with subacromial shoulder conditions (SSCs). Clinical decision-making regarding the best treatment option is often difficult. This study aims to evaluate the comparative effectiveness of treatment options for relieving pain and improving function in patients with SSCs. Methods: Eight databases [including MEDLINE, Embase, CINAHL, AMED, PEDro, Cochrane Database of Systematic Reviews and World Health Organization (WHO) International Clinical Trials Registry] were searched from inception until April 2020. Randomised clinical/controlled trials of adult patients investigating the effects of nonsurgical (e.g. corticosteroid injections, therapeutic exercise, shockwave therapy) and surgical treatment for SSCs, compared with each other, placebo, usual care or no treatment, were retrieved. Pairs of reviewers screened studies independently, quality appraised eligible studies using the Cochrane risk of bias tool, extracted and checked data for accuracy. Primary outcomes were pain and disability in the short term (⩽3 months) and long term (⩾6 months). Direct and indirect evidence of treatment effectiveness was synthesised using random-effects network meta-analysis. Results: The review identified 177 eligible trials. Summary estimates (based on 99 trials providing suitable data, 6764 patients, 20 treatment options) showed small to moderate effects for several treatments, but no significant differences on pain or function between many active treatment comparisons. The primary analysis indicated that exercise and laser therapy may provide comparative benefit in terms of both pain and function at different follow-up time-points, with larger effects found for laser in the short term at 2–6 weeks, although direct evidence was provided by one trial only, and for exercise in the longer term [standardised mean difference (SMD) 0.39, 95% confidence interval (CI) 0.18, 0.59 at 3–6 months] compared with control. Sensitivity analyses excluding studies at increased risk of bias confirmed only the comparative effects of exercise as being robust for both pain and function up until 3-month follow-up. Conclusion: Current evidence shows small to moderate effect sizes for most treatment options for SSCs. Six treatments had a high probability of being most effective, in the short term, for pain and function [acupuncture, manual therapy, exercise, exercise plus manual therapy, laser therapy and Microcurrent (MENS) (TENS)], but with low certainty for most treatment options. After accounting for risk of bias, there is evidence of moderate certainty for the comparative effects of exercise on function in patients with SSCs. Future large, high-quality pragmatic randomised trials or meta-analyses are needed to better understand whether specific subgroups of patients respond better to some treatments than others.