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Background Despite recommendations supporting optimal breastfeeding, the number of women practicing exclusive breastfeeding (EBF) remains low, and few interventions have demonstrated implementation and impact at scale. Alive & Thrive was implemented over a period of 6 y (2009–2014) and aimed to improve breastfeeding practices through intensified interpersonal counseling (IPC), mass media (MM), and community mobilization (CM) intervention components delivered at scale in the context of policy advocacy (PA) in Bangladesh and Viet Nam. In Bangladesh, IPC was delivered through a large non-governmental health program; in Viet Nam, it was integrated into government health facilities. This study evaluated the population-level impact of intensified IPC, MM, CM, and PA (intensive) compared to standard nutrition counseling and less intensive MM, CM, and PA (non-intensive) on breastfeeding practices in these two countries. Methods and Findings A cluster-randomized evaluation design was employed in each country. For the evaluation sample, 20 sub-districts in Bangladesh and 40 communes in Viet Nam were randomized to either the intensive or the non-intensive group. Cross-sectional surveys (n ~ 500 children 0–5.9 mo old per group per country) were implemented at baseline (June 7–August 29, 2010, in Viet Nam; April 28–June 26, 2010, in Bangladesh) and endline (June 16–August 30, 2014, in Viet Nam; April 20–June 23, 2014, in Bangladesh). Difference-in-differences estimates (DDEs) of impact were calculated, adjusting for clustering. In Bangladesh, improvements were significantly greater in the intensive compared to the non-intensive group for the proportion of women who reported practicing EBF in the previous 24 h (DDE 36.2 percentage points [pp], 95% CI 21.0–51.5, p < 0.001; prevalence in intensive group rose from 48.5% to 87.6%) and engaging in early initiation of breastfeeding (EIBF) (16.7 pp, 95% CI 2.8–30.6, p = 0.021; 63.7% to 94.2%). In Viet Nam, EBF increases were greater in the intensive group (27.9 pp, 95% CI 17.7–38.1, p < 0.001; 18.9% to 57.8%); EIBF declined (60.0% to 53.2%) in the intensive group, but less than in the non-intensive group (57.4% to 40.6%; DDE 10.0 pp, 95% CI −1.3 to 21.4, p = 0.072). Our impact estimates may underestimate the full potential of such a multipronged intervention because the evaluation lacked a “pure control” area with no MM or national/provincial PA. Conclusions At-scale interventions combining intensive IPC with MM, CM, and PA had greater positive impacts on breastfeeding practices in Bangladesh and Viet Nam than standard counseling with less intensive MM, CM, and PA. To our knowledge, this study is the first to document implementation and impacts of breastfeeding promotion at scale using rigorous evaluation designs. Strategies to design and deliver similar programs could improve breastfeeding practices in other contexts. Trial registration ClinicalTrials.gov NCT01678716 (Bangladesh) and NCT01676623 (Viet Nam), Phuong Nguyen and colleagues present a cluster-randomized program evaluation of strategies combining intensive interpersonal counseling, mass media, and community mobilization to improve breastfeeding practices., Author Summary Why Was This Study Done? The benefits of exclusive breastfeeding are well documented, but only about a third of infants are exclusively breastfed during their first 6 months of life, well short of the 50% target endorsed by the World Health Assembly. Past efforts to promote and support breastfeeding were rarely implemented at scale. Previous studies on strategies to support breastfeeding have been limited to efficacy research; the few studies of programmatic approaches did not use a rigorous evaluation design. What Did the Researchers Do and Find? We conducted two cluster-randomized impact evaluations of at-scale programs, in Bangladesh and Viet Nam (the Alive & Thrive initiative), to compare the population-level impacts on breastfeeding practices of two intervention packages: (1) an intensive package consisting of intensified interpersonal communication on breastfeeding, a mass media campaign, community mobilization, and policy advocacy to create a supportive environment for optimal breastfeeding practices and (2) a non-intensive package consisting of standard nutrition counseling on breastfeeding and a less intensive mass media campaign, community mobilization, and policy advocacy. Surveys were conducted among households with children 0–5.9 mo of age at two points in time, before the interventions started (2010) and four years later (2014). In both countries, we found significantly positive population-level impacts on breastfeeding practices, including higher rates of early initiation of breastfeeding and exclusive breastfeeding, and lower use of prelacteal feeding and bottle feeding, in areas that received the intensive package compared to areas that received the non-intensive package. What Do These Findings Mean? These findings provide much-needed evidence on what works to improve breastfeeding at scale. Combining interpersonal counseling of mothers on optimal breastfeeding practices with a mass media campaign is more effective than a mass media campaign alone, suggesting that using multiple platforms and interventions to improve breastfeeding practices leads to greater improvements in practices than using one strategy alone. The well-documented approach used by Alive & Thrive offers several implementation tools that can be used and adapted to inform the design of contextually relevant interventions to improve breastfeeding, a critical human development intervention.