IMPORTANCE Although 80% of infants in the United States start breastfeeding, only 22% are exclusively breastfed up to around 6 months as recommended by a number of professional organizations. OBJECTIVE To systematically review the evidence on the benefits and harms of breastfeeding interventions to support the US Preventive Services Task Force in updating its 2008 recommendation. DATA SOURCES MEDLINE, PubMed, Cumulative Index for Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, and PsycINFO for studies published in the English language between January 1, 2008, and September 25, 2015. Studies included in the previous review were re-evaluated for inclusion. Surveillance for new evidence in targeted publications was conducted through January 26, 2016. STUDY SELECTION Review of randomized clinical trials and before-and-after studies with concurrent controls conducted in a developed country that evaluated a primary care-relevant breastfeeding intervention among mothers of full-or near-term infants. Of 211 full-text articles reviewed, 52 studies met inclusion criteria. Thirty-one studies were newly identified, and 21 studies were carried forward from the previous review. DATA EXTRACTION AND SYNTHESIS Independent critical appraisal of all provisionally included studies. Data were independently abstracted by one reviewer and confirmed by another. MAIN OUTCOMES AND MEASURES Child and maternal health outcomes, rates and duration of breastfeeding, and harms related to interventions as prespecified before data collection. RESULTS Fifty-twostudies(n = 66 757)in57publicationswereincluded.Sixtrials(n = 2219)reported inconsistent effects of the interventions on infant health outcomes; no studies reported maternal health outcomes. Pooled estimates based on random-effects meta-analyses using the DerSimonian and Laird method indicated beneficial associations between individual-level breastfeeding interventions and any breastfeeding for less than 3 months (risk ratio [RR], 1.07 [95% CI, 1.03-1.11]; 26 studies [n = 11 588]), at 3 to less than 6 months (RR, 1.11 [95% CI, 1.04-1.18]; 23 studies [n = 8942]), and for exclusive breastfeeding for less than 3 months (RR, 1.21 [95% CI, 1.11-1.33]; 22 studies [n = 8246]), 3 to less than 6 months (RR, 1.20 [95% CI, 1.05-1.38]; 18 studies [n = 7027]), and at 6 months (RR, 1.16 [95% CI, 1.02-1.32]; 17 studies [n = 7690]). Absolute differences in the rates of any breastfeeding ranged from 14.1% in favor of the control group to 18.4% in favor of the intervention group. There was no significant association between interventions and breastfeeding initiation (RR, 1.00 [95% CI, 0.99-1.02]; 14 studies [n = 9428]). There was limited mixed evidence of an association between system-level interventions and rates of breastfeeding from well-controlled studies as well as for harms related to breastfeeding interventions, including maternal anxiety scores, decreased confidence, and concerns about confidentiality. CONCLUSIONS AND RELEVANCE The updated evidence confirms that b...