The extraskeletal role of vitamin D is being increasingly recognised. This has important clinical implications, as vitamin D deficiency has reached epidemic proportions worldwide. Vitamin D has proposed anti-inflammatory properties, yet the role of vitamin D supplementation in reducing inflammation remains largely unknown. The purpose of this review is to investigate the impact of vitamin D supplementation on inflammation, and to identify relevant knowledge gaps in the field.Medline, CINAHL, EMBASE and All EBM will be systematically searched for randomised controlled trials (RCTs) and systematic reviews of RCTs, comparing vitamin D supplementation with placebo, usual care or other pharmacological or non-pharmacological interventions. One reviewer will assess articles for eligibility according to prespecified selection criteria, after which 2 independent reviewers will perform data extraction and quality appraisal. Meta-analyses will be conducted where appropriate.Formal ethical approval is not required as no primary data is collected. This systematic review will identify potential clinical implications of vitamin D deficiency and supplementation, and will be disseminated through a peer-reviewed publication and at conference meetings, to inform future research on the efficacy of vitamin D supplementation for inflammation and inflammatory diseases.CRD42016037104.