Aims: The current review aimed to systematically identify, evaluate and synthesise evidence from randomised controlled trials (RCTs) on the effectiveness of interventions for prevention of neck pain. Methods: We searched the literature using MEDLINE, EMBASE, CINAHL, Physiotherapy Evidence Database, and The Cochrane Central Register of Controlled Trials (CENTRAL). We assessed RCTs of strategies to prevent neck pain, which enrolled participants without current neck pain at study entry. Eligibility criteria were assessed by two independent reviewers. Data extraction and risk of bias assessments were completed by two independent reviewers. Random-effects meta-analysis was used to pool data. The GRADE approach was used to evaluate the overall quality of evidence. The main outcome was reduction in risk of a new episode of neck pain. Odds ratios (OR) and 95% confidence interval (CI) were calculated using random-effect models. Results: Five trials including a total of 3,852 individuals were eligible. The pooled results, from two RCTs (500 participants), found moderate-quality evidence that exercise reduces the risk of a new episode of neck pain (OR, 0.32; 95% CI, 0.12 to 0.86). One of the meta-analysed trials included some co-interventions with the exercise. There is low-quality evidence from 3 RCTs (3,352 participants) that ergonomic programs do not reduce the risk of a new neck pain episode (OR, 1.00; 95% CI, 0.74 to 1.35). Conclusions: We found moderate-quality evidence supporting the effectiveness of exercise for reducing the risk of a new episode of neck pain. High-quality RCTs evaluating interventions to prevent new episodes of neck pain are needed.