ImportanceCurrent evidence on the association between family history of psychiatric disorders and postpartum depression is inconsistent; family studies have identified familial risk of postpartum depression, whereas systematic reviews and umbrella reviews, compiling all risk factors for postpartum depression, often have not.ObjectiveTo investigate the association between family history of psychiatric disorders and risk of developing postpartum depression within 12 months post partum.Data SourcesLiterature searches were conducted in PubMed, Embase, and PsycINFO in September 2021 and updated in March 2022, accompanied by citation and reference search.Study SelectionStudies eligible for inclusion comprised peer-reviewed cohort and case-control studies reporting an odds ratio (OR) or sufficient data to calculate one for the association between family history of any psychiatric disorder and postpartum depression. Study selection was made by 2 independent reviewers: title and abstract screening followed by full-text screening.Data Extraction and SynthesisReporting was performed using the MOOSE checklist. Two reviewers independently extracted predefined information and assessed included studies for risk of bias using the Newcastle-Ottawa Scale. Data were pooled in a meta-analysis using a random-effects model. Heterogeneity was investigated with meta-regression, subgroup, and sensitivity analyses. Publication bias was investigated using a funnel plot, and GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to evaluate the overall certainty of the findings.Main Outcomes and MeasuresThe primary outcome was the pooled association between family history of psychiatric disorders and postpartum depression.ResultsA total of 26 studies were included, containing information on 100 877 women. Meta-analysis showed an increased OR of developing postpartum depression when mothers had a family history of psychiatric disorders (OR, 2.08; 95% CI, 1.67-2.59; I2 = 57.14%) corresponding to a risk ratio of 1.79 (95% CI, 1.52-2.09), assuming a 15% postpartum depression prevalence in the general population. Subgroup, sensitivity, and meta-regression analyses were in line with the primary analysis. The overall certainty of evidence was deemed as moderate according to GRADE.Conclusions and RelevanceIn this study, there was moderate certainty of evidence for an almost 2-fold higher risk of developing postpartum depression among mothers who have a family history of any psychiatric disorder compared with mothers without.