BACKGROUND: Applications emitting radiofrequency electromagnetic fields (RF-EMF; 100 kHz to 300 GHz) are widely used for communication (e.g. mobile phones), in medicine (diathermy) and in industry (RF heaters). OBJECTIVES: The objective is to systematically review the effects of longer-term or repeated local and whole human body radiofrequency electromagnetic field (RF-EMF) exposure on the occurrence of symptoms. Primary hypotheses were tinnitus, migraine and headaches in relation to RF-EMF exposure of the brain, sleep disturbances and composite symptom scores in relation to whole-body RF-EMF exposure. METHODS: Eligibility criteria: We included case-control and prospective cohort studies in the general population or workers estimating local or whole-body RF-EMF exposure for at least one week. INFORMATION SOURCES: We conducted a systematic literature search in various databases including Web of Science and Medline. Risk of bias: We used the Risk of Bias (RoB) tool developed by OHAT adapted to the topic of this review. SYNTHESIS OF RESULTS: We synthesized studies using random effects meta-analysis. RESULTS: Included studies: We included 13 papers from eight distinct cohort and one case-control studies with a total of 486,558 participants conducted exclusively in Europe. Tinnitus is addressed in three papers, migraine in one, headaches in six, sleep disturbances in five, and composite symptom scores in five papers. Only one study addressed occupational exposure. SYNTHESIS OF RESULTS: For all five priority hypotheses, available research suggests that RF-EMF exposure below guideline values does not cause symptoms, but the evidence is very uncertain. The very low certainty evidence is due the low number of studies, possible risk of bias in some studies, inconsistencies, indirectness, and imprecision. In terms of non-priority hypotheses numerous exposure-outcome combinations were addressed in the 13 eligible papers without indication for an association related to a specific symptom or exposure source. DISCUSSION: Limitations of evidence: This review topic includes various challenges related to confounding control and exposure assessment. Many of these aspects are inherently present and not easy to be solved in future research. Since near-field exposure from wireless communication devices is related to lifestyle, a particular challenge is to differentiate between potential biophysical effects and other potential effects from extensive use of wireless communication devices that may compete with healthy behaviour such as sleeping or physical activity. Future research needs novel and innovative methods to differentiate between these two hypothetical mechanisms. INTERPRETATION: This is currently the best available evidence to underpin safety of RF-EMF. There is no indication that RF-EMF below guideline values causes symptoms. However, inherent limitations of the research results in substantial uncertainty. OTHER: Funding: This review was partially funded by the WHO radioprotection programme. REGISTRATION: The protocol for this review has been registered in Prospero (reg no CRD42021239432) and published in Environment International (Röösli et al., 2021).