OBJECTIVE To investigate a possible association between the intensity of staff workload and intermediate adverse events, such as accidental extubation, obstruction of the endotracheal tube, and accidental disconnection of the ventilator circuit, during neonatal mechanical ventilation in high-risk neonatal units. METHODS This prospective cohort study analyzed data of 543 newborns from public neonatal intensive care units (NICUs) in the city of São Luís, state of Maranhão, Northeastern Brazil, for 6 months, during which 136 newborns were submitted to mechanical ventilation in 1,108 shifts and were observed a total of 4,554 times. RESULTS Adverse events occurred 117 times during this period. The associations between workload and adverse events were analyzed by means of generalized estimating equations. The adjustment variables were: birth weight, gender, maternity unit, Clinical Risk Index for Babies score, and care demand, the latter measured by the Northern Neonatal Network Scale. The larger the number of newborns classified by care demand (NCCD) per nurse and nursing technician, the more likely the occurrence of intermediate adverse events linked to mechanical ventilation. A number of NCCD > 22 per nurse (relative risk [RR] = 2.86) and > 4.8 per auxiliary nurse (RR = 3.41) was associated with a higher prevalence of intermediate adverse events. CONCLUSIONS The workload of NICU professionals seems to interfere with the intermediate results of neonatal care and thus should be taken into consideration when evaluating NICU outcomes.