Value-based health insurance designs (VBIDs) are one approach to increase adherence to highly effective medications and simultaneously contain rising health care costs. The objective of this systematic review was to identify VBID effects on adherence and incentive designs within these programs that were associated with higher effects. Eight economic and medical databases were searched for literature. Random effects meta-analyses and mixed effects meta-regressions were used to synthesize VBID effects on adherence. Thirteen references with evaluation studies, including 12 patient populations with 79 outcomes, were used for primary meta-analyses. For qualitative review and sensitivity analyses, up to 19 references including 20 populations with 119 outcomes were used. Evidence of synthesized effects was good, because references with high risk of bias were excluded. VBIDs significantly increased adherence in all indication areas. Highest effects were found in medications indicated in heart diseases (4.05%-points, p < 0.0001). Each additional year increased effects by 0.15%-points (p < 0.01). VBIDs with education were more effective than without education, but the difference was not significant. Effects of VBIDs with full coverage were more than twice as high as effects of VBID without that option (4.52 vs 1.81%-points, p < 0.05). These findings were robust in most sensitivity analyses. It is concluded that VBID implementation should be encouraged, especially for patients with heart diseases, and that full coverage was associated with higher effects. This review may provide insight for policy-makers into how to make VBIDs more effective.