ImportanceUnintended pregnancy is common in the US and is associated with adverse maternal and infant health outcomes; however, estimates of these associations specific to current US populations are lacking.ObjectiveTo evaluate associations of unintended pregnancy with maternal and infant health outcomes during pregnancy and post partum with studies relevant to current clinical practice and public health in the US.Data SourcesCochrane Central Register of Controlled Trials and Database of Systematic Reviews, PsycINFO, SocINDEX, and MEDLINE databases (January 1, 2000, to June 15, 2022) and manual review of reference lists.Study SelectionEpidemiologic studies relevant to US populations that compared key maternal and infant health outcomes for unintended vs intended pregnancies and met prespecified eligibility criteria were included after investigators’ independent dual review of abstracts and full-text articles.Data Extraction and SynthesisInvestigators abstracted data from publications on study methods, participant characteristics, settings, pregnancy intention, comparators, confounders, and outcomes; data were validated by a second investigator. Risk of bias was independently dual rated by investigators using criteria developed by the US Preventive Services Task Force. Results of studies controlling for confounders were combined by using a profile likelihood random-effects model.Main Outcomes and MeasuresPrenatal depression, postpartum depression, maternal experience of interpersonal violence, preterm birth, and infant low birth weight.ResultsThirty-six studies (N = 524 522 participants) were included (14 cohort studies rated good or fair quality; 22 cross-sectional studies); 12 studies used large population-based data sources. Compared with intended pregnancy, unintended pregnancy was significantly associated with higher odds of depression during pregnancy (23.3% vs 13.9%; adjusted odds ratio [aOR], 1.59 [95% CI, 1.35-1.92]; I2 = 85.0%; 15 studies [n = 41 054]) and post partum (15.7% vs 9.6%; aOR, 1.51 [95% CI, 1.40-1.70]; I2 = 7.1%; 10 studies [n = 82 673]), interpersonal violence (14.6% vs 5.5%; aOR, 2.22 [95% CI, 1.41-2.91]; I2 = 64.1%; 5 studies [n = 42 306]), preterm birth (9.4% vs 7.7%; aOR, 1.21 [95% CI, 1.12-1.31]; I2 = 1.7%; 10 studies [n = 94 351]), and infant low birth weight (7.3% vs 5.2%; aOR, 1.09 [95% CI, 1.02-1.21]; I2 = 0.0%; 8 studies [n = 87 547]). Results were similar in sensitivity analyses based on controlling for history of depression for prenatal and postpartum depression and on study design and definition of unintended pregnancy for relevant outcomes. Studies provided limited sociodemographic data and measurement of confounders and outcomes varied.Conclusions and RelevanceIn this systematic review and meta-analysis of epidemiologic observational studies relevant to US populations, unintended pregnancy, compared with intended pregnancy, was significantly associated with adverse maternal and infant outcomes.Trial RegistrationPROSPERO Identifier: CRD42020192981