Patient portals are offered by health care organizations to facilitate health information sharing and patient empowerment and support patient-centered care. The aim of this systematic review is to assess the effect of patient portals on patient empowerment and health-related outcomes. After a systematic literature search, ten randomized controlled trials (RCTs) were included in this review. Of these, seven RCTs were conducted in the United States., two in Canada, and one in Japan. Study characteristics, risk of bias, and outcomes were extracted. varied in terms of intervention, included patients, and outcome. Most studies found no or only a small, clinically non-relevant effect of patient portals. The review showed that future research should develop a taxonomy to describe patient portal functionalities to facilitate the aggregation of evidence.