Potential barriers to intrauterine device (IUD) use include provider concern about difficult insertion, particularly for nulliparous women.This study aims to evaluate the evidence on the effectiveness of medications to ease IUD insertion on provider outcomes (i.e., ease of insertion, need for adjunctive insertion measures, insertion success).We searched the PubMed database for peer-reviewed articles published in any language from database inception through February 2016.We included randomized controlled trials (RCTs) that examined medications to ease interval insertion of levonorgestrel-releasing IUDs and copper T IUDs.From 1855 articles, we identified 15 RCTs that met our inclusion criteria. Most evidence suggested that misoprostol did not improve provider ease of insertion, reduce the need for adjunctive insertion measures or improve insertion success among general samples of women seeking an IUD (evidence Level I, good to fair). However, one RCT found significantly higher insertion success among women receiving misoprostol prior to a second IUD insertion attempt after failed attempt versus placebo (evidence Level I, good). Two RCTs on 2% intracervical lidocaine as a topical gel or injection suggested no positive effect on provider ease of insertion (evidence Level I, good to poor), and one RCT on diclofenac plus 2% intracervical lidocaine as a topical gel suggested no positive effect on provider ease of insertion (evidence Level I, good). Limited evidence from two RCTs on nitric oxide donors, specifically nitroprusside or nitroglycerin gel, suggested no positive effect on provider ease of insertion or need for adjunctive insertion measures (evidence Level I, fair).Overall, most studies found no significant differences between women receiving interventions to ease IUD insertion versus controls. Among women with a recent failed insertion who underwent a second insertion attempt, one RCT found improved insertion success among women using misoprostol versus placebo.