Despite the increasing availability of online patient portals that provide access to electronic health records, little is known about their adoption by patients. We systematically reviewed the literature to investigate adoption of patient portals across studies. We searched MEDLINE and Scopus to identify relevant papers. We included 40 studies: 24 were controlled experiments, with prospective data collection in an actively recruited population; 16 were real-world experiments, with adoption being evaluated retrospectively after system deployment in clinical practice. Our meta-analysis showed an overall mean adoption rate of 52% (95% Confidence Interval [CI], 42 to 62%). Rates differed markedly between study types: controlled experiments yielded a mean adoption rate of 71% (95% CI 64 to 79%), compared to 23% (95% CI, 13 to 33%) in real-world experiments. This difference was confirmed in a meta-regression analysis of the influence of study characteristics on adoption rates. Our findings suggest that adoption rates reported in controlled studies do not reflect those in everyday clinical practice. Until we understand how to effectively increase adoption, patient portals are unlikely to consistently lead to improvements in care processes and health outcomes.