Abstract Background Though previous research repeatedly found that being employed is better for health than having no job at all, evidence suggests that employment is not always beneficial for health. With especially job insecurity reflecting a contemporary health risk for the employed, a systematic review was performed to assess if insecure employment can be as detrimental for health as unemployment, and to determine whether these associations vary according to different health measures and among men and women. Methods The literature search was conducted in the databases Medline, Embase and PsychInfo. In order to allow a more accurate comparison between the two risk factors, studies were included if the data for job insecurity and unemployment was ascertained from the same sample, and contained a quantitative analysis for both exposures towards one (or more) health outcome(s). Results Out of 375 articles, in total, 13 studies were included in the systematic review. In 24 analyses contrasting the health-related associations between job insecurity and unemployment, 16 statistically significant associations were found for each exposure. According to the different health outcomes used, job insecurity and unemployment were strongly related to mental health, whereas job insecurity was more strongly associated with somatic symptoms. Unemployment showed stronger relations with worse general health and mortality. In 4 out of 16 gender-stratified analyses, significant associations between job insecurity/unemployment and health were found for men but not for women. Beyond that, associations were significant or insignificant in both gender groups. Conclusions Though there were moderate differences across the health outcomes, overall, it was found that job insecurity can pose a comparable threat to health than unemployment. Policy interventions should therefore not only consider health risks posed by unemployment, but should also aim at the reduction of insecure employment.