MotherSafe is a free telephone-based counseling service for Australian consumers and health-care providers concerned about drug exposures during pregnancy and breastfeeding. Anti-infectives are the most commonly prescribed drugs for pregnant women. This study aims to provide a descriptive analysis of prospectively collected calls received by MotherSafe regarding anti-infective exposures during pregnancy between 2000 and 2020. Aggregate data were examined by type of caller, reason for call, pregnancy category and exposure type. Inductive thematic analysis of the comments recorded by MotherSafe counsellors at the time of call was undertaken. Over the study period, 25,890 calls related to exposure to anti-infectives during pregnancy (antibiotic, antiviral, and antifungal medications). Calls from patients were dominated by low-risk exposures (pregnancy category A) to drugs while calls from health care professionals related to drugs with limited human information (pregnancy category B3). Analysis of MotherSafe counsellor comments revealed over 200 instances of concerns relating to health care professional advice to the patient. Three themes emerged: incorrect or conflicting advice, poor counselling, and refusal to treat, prescribe or dispense. It is likely that these comments are biased to the negative as patients would not call MotherSafe if they were happy with HCP advice. However, the findings are concerning as they reveal an underlying lack of knowledge in some health care professionals which may have led to undertreatment of patients. This study reinforced the importance of Teratogen Information Services such as MotherSafe in providing counselling and clear communication of evidence-based information to guide decision-making, reducing potential emotional distress in pregnant women, and optimizing maternal, pregnancy and infant outcomes.