Background: In December 2006, Seguro Popular (SP) implemented the Medical Insurance Century XXI program (SMSXXI) to provide public healthcare insurance to children under five years old who lack social security. SMSXXI aims to increase access to health services, reduce out-of-pocket health-related expenditures (OOPHE), and lower health inequities. Methods: We assessed the effects of SMSXXI on health outcomes and financial protection for Mexico's children using multiple nationally representative surveys and administrative data sources spanning the period between 2001 and 2016. The identification of effects relied on detailed hospital level affiliation data mapping the geographical expansion of the program's coverage across the country over time. The final outcomes were neonatal and infant mortality, self-reported morbidity (health status, flu, and diarrhea) and child's height. Intermediate outcomes were OOPHE, hospital discharges and quality of service provision. Effects controlled for fixed and time-variant confounders using double- and triple-difference estimation strategies. Where feasible, we also estimated effects using exogenous variation in program eligibility rules that limited enrollment in SMSXXI to children born after December 1, 2006. Findings: SMSXXI reduced the infant mortality rates of conditions covered by the program by 5.3%. The effects were largest in high baseline mortality areas. Long-run health effects, eight years after the onset of SMSXXI, were reflected in a 0.44 cm average increase in height for birth cohorts exposed to the program, and an average effect on height of almost 1cm for low-income populations. Approximately three to six years after the program started, children reported having better health status and lower incidence of the flu and diarrhea. The program led to a 10% reduction in OOPHE, primarily from hospital-related expenses. No effects were detected on hospital discharges, suggesting that the program may not have increased utilization. Rather, improvements in the quality of healthcare and specialized personnel are likely channels driving improvements in health outcomes. Interpretation: SMSXXI covers uninsured, primarily low-income populations who may be most at risk from the financial and health consequences of costly medical interventions. The program transfers resources from the federal level to states and providers for the enrollment and treatment of children under five years old. Transfers are conditioned on the compliance of medical facilities with accreditation standards (criteria of capacity, quality and safety for the patient). Funds are used to strengthen local health services through the purchase of equipment and staffing of medical specialists. We use previously unexploited sources of exogenous variation in program assignment to identify causal effects on health and financial risk. Results suggest that SMSXXI reduced infant mortality, improved long-run health as proxied by self-reported morbidity and child height, and protected low-income families from the adverse economic consequences of health shocks. Funding: Funding for this study was provided through Inter-American Development Bank (IDB) Technical Cooperation ME-T1307. Declaration of Interest: Dr. Celhay has nothing to disclose. Dr. Martinez has nothing to disclose. Mr. Munoz has nothing to disclose. Mrs. Perez has nothing to disclose. Dr. Perez Cuevas has nothing to disclose. Ethical Approval: The study consists in a secondary data analysis of several databases; all these databases have the de-identified data; thus, it is not possible to trace any of the data to the actual individual. In accordance to the Internal Regulation of the Interamerican Development Bank, this secondary data analysis can be considered exempt of institutional review board approval.