Background: Adverse Drug Reaction (ADR) is a public health problem with an impact on health care costs. Spontaneous reporting comprises the primary method for detection ADR’s. However, high levels under-reporting represents a barrier in pharmacovigilance. Objectives: The present study aims to estimate the prevalence of under-reporting ADR professionals in Brazil and to analyze the factors associated with under-reporting. Methods: Used a cross-sectional study based on an online survey for healthcare professionals conducted by the Brazilian Health Regulatory Agency (Anvisa). Unconditional logistic regression was performed and adjusted odd ratios (OR) were estimated. Results: In total 789 questionnaires were analyzed and based on the criteria, 67.5% of professionals were considered under-reporters. The main reason for under-reporting was the lack of access to vital data for notification (33.8%). 52.7% of the participants stated that the existence of a simpler system to notify motivated its use. It was found that residents in the Southern region of Brazil have 2.3 times the chance of under-reporting an ADR than those in the Southeast region (OR = 2.3; IC 95%:1.3-4.2). Having advanced knowledge in pharmacovigilance (OR=0.5; IC 95%: 0.4-0.7) and performing notification even without the causal certainty of the event (OR = 0.5; IC 95%:0.3-0.7) were protective factors for under-reporting, while not applicating knowledge routinely was considered a risk factor for under-reporting (OR = 4.4; IC 95%:2.1-9.2). Conclusion: A high rate of professionals considered as under-reporters of ADRs in Brazil has been detected. This study will make an important contribution to health managers and drug regulators for strengthen the national pharmacovigilance system.