BACKGROUND : Pressures on the health care system are a stimulus for innovation, including workforce changes such as substitution. A common approach to substitution in primary care is where nurses replace medical staff in roles traditionally filled by physicians. However, questions regarding the safety and effectiveness of substitution remain. The objective of this systematic review was to evaluate outcomes from nurse substitution in primary health care settings. METHODS : The review of randomised controlled trials used Cochrane methods to evaluate study quality (risk of bias) and select papers focused on nurse substitution in primary care. Two independent reviewers were used for each key step, following a comprehensive search in this high quality systematic review. RESULTS : Eighteen studies were included, showing clinical outcomes were comparable (and not worse) when nurses substituted for medical staff. While nurses were reliably found to spend more time per consult, this was the only significant difference between nurses and physicians; with data on patient outcomes being similar. CONCLUSIONS : Nurses in primary care are safe, effective first contact providers who can sustain ongoing patient management without adversely effecting healthcare outcomes.