Supplemental screening with MRI or ultrasound increases cancer detection rate (CDR) in women with standard screening mammography. Whether it also reduces interval cancer rate (ICR) is unclear. This study reviewed the evidence evaluating the effect of supplemental imaging on ICR in women undergoing screening mammography. This systematic review included studies that reported both CDR and ICR in women undergoing screening mammography alone compared to those undergoing screening mammography with supplemental imaging. Five studies (3 randomized trials) were eligible. These reported on 142,153 women undergoing mammography screening alone or mammography with supplemental imaging (3 ultrasound and 2 MRI studies). Two studies included a general screening population and 3 included special populations (young, high genetic risk and/or dense breasts). The incremental CDR for supplemental MRI was 14.2 to 16.5/1000 screens and for ultrasound was 0 to 4.4/1000 screens. Effect on ICR was variable but evidence of a reduced ICR was more consistent for studies using supplemental MRI (ICR 0.3 to 0.8 per 1000 screens) than those using ultrasound (ICR 0.49 to 1.9 per 1000 screens). The higher CDR and lower ICR with supplemental screening were associated with higher recall and biopsy rates particularly with supplemental MRI (9.5%-15.9%, up to 69/1000 screens). Cancers detected with supplemental imaging modalities were generally smaller and earlier stage. Mammography with supplemental MRI or ultrasound increases detection of cancers (versus mammography only) in some sub-groups but also increases recall and biopsy rates and may have a relatively modest effect in reducing ICR.