It has been suggested that receiving a negative screening test result may cause false reassurance or have a 'certificate of health effect'. False reassurance in those receiving a negative screening test result may result in them wrongly believing themselves to be at lower risk of the disease, and consequently less likely to engage in health-related behaviours that would lower their risk. The present systematic review aimed to identify the evidence regarding false reassurance effects due to negative screening test results in adults (over 18 years) screened for the presence of a disease or its precursors, where disease or precursors are linked to lifestyle behaviours. MEDLINE and PsycINFO were searched for trials that compared a group who had received negative screening results to an unscreened control group. The following outcomes were considered as markers of false reassurance: perceived risk of disease; anxiety and worry about disease; health-related behaviours or intention to change health-related behaviours (i.e., smoking, diet, physical activity, and alcohol consumption); self-rated health status. Nine unique studies were identified, reporting 55 measures in relation to the outcomes considered. Outcomes were measured at various time points from immediately following screening to up to 11 years after screening. Despite considerable variation in outcome measures used and timing of measurements, effect sizes for comparisons between participants who received negative screening test results and control participants were typically small with few statistically significant differences. There was evidence of high risk of bias, and measures of behaviours employed were often not valid. The limited evidence base provided little evidence of false reassurance following a negative screening test results on any of four outcomes examined. False reassurance should not be considered a significant harm of screening, but further research is warranted. Statement of contribution What is already known on this subject? It has been argued that screening for disease may cause 'false reassurance' whereby those who receive a negative screening test result wrongly interpret their result as indicating they are less likely to develop the disease in future. There is some evidence for false reassurance, but the relevant studies consider a range of diseases and possible indicators of false reassurance (i.e., risk perceptions, lifestyle behaviours, emotional outcomes, and quality of life). For these reasons, it is currently unclear that the extent to receive negative screening test results is likely to impact on participants' lifestyle behaviours, or other possible indicators of false reassurance. What does this study add? Current available evidence shows that negative screening test results are unlikely to cause false reassurance and, in particular, are unlikely to have a negative impact on lifestyle behaviours. Given the limitations of the current evidence base in terms of number of studies and study quality, future research should continue to explore this issue, where this can be done at low cost.