Background: Team-Based Learning (TBL) is a student-centred active learning method, requiring less faculty time than other active learning methods. While TBL may have pedagogical value, individual studies present inconsistent findings. The aim of this systematic review was to assess the effectiveness of TBL on improving learning outcomes in health professions education. Methods: A peer-reviewed systematic review protocol was registered with the Best Evidence in Medical Education (BEME) organization. After comprehensive literature searching, title and full-text review were completed by two independent reviewers. Included studies assessed TBL and a valid comparator in health professions. Included studies were assessed for methodological quality by two independent reviewers. Studies were categorised by outcomes using the Kirkpatrick framework. Results: Of 330 screened titles, 14 were included. Seven studies reported significant increase in knowledge scores for the TBL group, four reported no difference and three showed improvement but did not comment on statistical significance. Only one study reported significant improvement in learner reaction for the TBL group while another study reported a significant difference favouring the comparator. Conclusions: Despite improvement in knowledge scores, there was mixed learner reaction. This may reflect the increased demands on learners in this student-centred teaching strategy, although further study is needed.