The spread and emergence of neuroinvasive circulating vaccine-derived polioviruses (cVDPVs) across multiple countries prompted the emergency introduction of the novel oral polio vaccine type 2 (nOPV2), raising renewed concerns about how adverse events following immunization (AEFI) are monitored. This study investigated the profile of AEFI associated with nOPV2 and explored stakeholder perspectives and operational challenges related to AEFI surveillance in Sierra Leone. A mixed-methods design was employed. We retrospectively analyzed routinely collected passive surveillance data from the 2021 vaccination campaign and complemented this with semi-structured interviews involving vaccinators, district AEFI focal personnel, and key actors from the national Expanded Program on Immunization and the National Medicines Regulatory Authority. Classification of AEFI was undertaken using MedDRA Preferred Terms (PTs) and System Organ Class (SOC). Patient outcomes were grouped into recovered versus not recovered. Causality was evaluated using the WHO algorithm, while preventability was assessed through the Schumock and Thornton framework. Overall, 528 suspected AEFI cases were documented, with most occurring in infants and young children aged 28 days to 23 months (63.3%). The most frequently affected categories were general disorders and administration site reactions, and pyrexia was the most commonly reported Preferred Term. Among 80 serious cases, 78 individuals recovered, and 74 cases were classified as having an inconsistent relationship with the vaccine. Most serious events (78) were judged as not preventable, while only two were considered possibly preventable. Routine AEFI reporting was not consistently practiced among study participants. There were inconsistencies in understanding what constituted a reportable event and uncertainty regarding reporting responsibilities. Additional barriers included challenges with the Open Data Kit (ODK) system and limited training opportunities. Although nOPV2 is a relatively new vaccine, the majority of reported AEFI were non-serious, and most serious cases were not found to be causally related to vaccination. However, notable variation existed among participants in terms of knowledge, practice, and awareness of AEFI reporting procedures.
