Abstract Background The use of financial incentives and penalties to encourage uptake of healthy behaviors is increasingly seen as a viable intervention in developed countries. Previous reviews of the effectiveness of financial incentives and penalties for encouraging the uptake of healthy behaviors have focused on individual behaviors making it difficult to draw overall conclusions about the effectiveness of such interventions. This systematic review will explore the effectiveness of financial incentives and penalties for encouraging a wide range of behaviors, including: smoking cessation, increased physical activity, healthier dietary intake, sensible patterns of alcohol consumption, safe sun, safe sex, and primary preventive clinical behaviors. Methods Systematic methods will be used to search existing literature and screen studies for inclusion. All studies that meet the following inclusion criteria will be included in the review: participants were 18 years old or older and living in high-income countries; interventions included cash or cash-like incentives to promote the uptake of healthy behaviors, or cash or cash-like penalties to discourage unhealthy behaviors; the comparator was usual care or no intervention; study design was randomized controlled trial, cluster randomized controlled trial, controlled before and after study, or interrupted time series analysis. Two reviewers will independently screen the publications to ensure they meet the inclusion criteria. Quality will be assessed by two researchers, working independently, using the Cochrane risk of bias tool. Meta-analysis will be conducted, if appropriate. Any studies identified as at ‘high risk of bias’ will be excluded from meta-analysis. Discussion This systematic review will provide policy-relevant recommendations for the use of financial incentives and penalties as a method of encouraging uptake of healthy behaviors.