BACKGROUND: Digital technology offers good opportunities for HIV prevention. This systematic review assesses the effectiveness of interactive digital interventions (IDIs) for prevention of sexually transmitted HIV. METHODS: We conducted a systematic search for randomized controlled trials (RCTs) of IDIs for HIV prevention, defining 'interactive' as producing personally tailored material. We searched databases including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsycINFO, grey literature, reference lists, and contacted authors if needed.Two authors screened abstracts, applied eligibility and quality criteria and extracted data. Meta-analyses used random-effects models with standardized mean differences (SMD) for continuous outcomes and odds ratios (OR) for binary outcomes, assessing heterogeneity using the I2 statistic. RESULTS: We included 31 RCTs of IDIs for HIV prevention. Meta-analyses of 29 RCTs comparing IDIs with minimal interventions (e.g. leaflet, waiting list) showed a moderate increase in knowledge (SMD 0.56, 95% CI 0.33 to 0.80), no effect on self-efficacy (SMD 0.13, 95% CI 0.00 to 0.27), a small improvement in intention (SMD 0.16, 95% CI 0.06 to 0.26), improvement in HIV prevention behaviours (OR 1.28, 95% CI 1.04 to 1.57) and a possible increase in viral load, but this finding is unreliable.We found no evidence of difference between IDIs and face-to-face interventions for knowledge, self-efficacy, intention, or HIV-related behaviours in meta-analyses of five small RCTs. We found no health economic studies. CONCLUSION: There is good evidence that IDIs have positive effects on knowledge, intention and HIV prevention behaviours. IDIs are appropriate for HIV prevention in a variety of settings.Supplementary Video Abstract, http://links.lww.com/QAD/B934.