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AMSTAR‐2 is a critical appraisal instrument for systematic reviews and may have a role in editorial processes. This study explored whether associations exist between AMSTAR‐2 assessments and editorial decisions. A retrospective, cross‐sectional study of manuscripts submitted to a single journal between 2015 and 2017 was undertaken. All submissions that reported an eligible systematic review were assessed using AMSTAR‐2 by two assessors. Inter‐rater agreement (IRR) was calculated for all AMSTAR‐2 items. Associations between AMSTAR‐2 assessments and the editorial decision, final publication status in any journal, and measures of impact were explored. One hundred and twenty‐two manuscripts were included. Across all AMSTAR‐2 items, the IRR varied from 0.03 (slight agreement) to 0.82 (substantial agreement). All submissions contained at least two critical methodological weaknesses. There was no difference in the number of weaknesses (median: 4; IQR: 3–5 vs. median: 4; IQR: 3.5–4.5; p = 0.482) between accepted and rejected submissions. Neither was there a difference between rejected submissions published elsewhere and those which remained unpublished (median: 4; IQR: 3.5–4.5 vs. median: 4; IQR: 4.5–5; p = 0.103). The number of weaknesses was not associated with academic impact. There was no association with AMSTAR‐2 assessments and editorial outcomes. Further work is required to explore whether the instrument can be prospectively operationalized for use during editorial processes.