To provide updated guidance on pre-conception folic acid and multivitamin supplementation for primary and secondary (recurrence) prevention of neural tube defects and other folate-sensitive congenital anomalies. Women aged 12-45 years who could become pregnant should be aware of the risk of serious birth defects without adequate pre-conception and first-trimester folic acid supplementation. Optimizing folic acid supplementation is complex and depends on factors including dosage; type of supplement; bioavailability of folate from food, timing of initiating supplementation; and metabolic and genetic factors. For all women who could become pregnant, a low daily dosage of folic acid is recommended before conception and throughout pregnancy and breastfeeding. High-dosage folic acid supplementation is recommended only for women who can become pregnant and have had a previous pregnancy affected by a neural tube defect or other folate-sensitive congenital anomaly. Directed personalized approaches could be considered and adopted for women who can become pregnant and have complex risks (genetic, medical, or surgical risk factors), using new knowledge of co-factor metabolism and synergy, as well as red blood cell or serum folate testing. Such approaches would require changes to current provincial health care maternal serum folate screening/testing. New approaches to oral folic acid supplementation, including triage tools, need to be considered to optimize the benefits of decreasing risk of neural tube defects and folate-sensitive congenital anomalies. Oral folic acid supplementation, or dietary folate intake combined with a multivitamin/micronutrient supplement, is associated with lower rates of neural tube defects, other folate-sensitive birth defects, and obstetrical complications. The costs are those attributable to daily vitamin supplementation and a healthy, folate-rich diet. A literature search was designed and carried in PubMed and the Cochrane Library databases from 1990 to 2021 using following MeSH terms and keywords (and variants): folic acid supplementation; folate food fortification; primary neural tube defect prevention; prevention of recurrence of neural tube defects; folate-sensitive birth defects; folate supplementation benefit; folate supplementation risk; folate pregnant woman physiology; pregnant woman RBC folate level; pregnant woman serum folate levels; folate and epilepsy; folate and obesity. This guideline was based upon expert guidelines or opinions, systematic reviews, randomized controlled clinical trials, and observational case-control studies and case series retrieved, published in English from 1990 to 2021. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). Maternity health care providers (physicians, midwives, nurses) and other providers of pregnancy-related wellness and health counselling.