The manifestation and spread of neuroinvasive circulating vaccine-derived polioviruses (cVDPVs) across several countries, which led to the emergency use of the novel oral polio vaccine type 2 (nOPV2), raised concerns about adverse events following immunization (AEFI) surveillance. We assessed the attributes of AEFI with nOPV2 and examined stakeholder experiences and challenges in AEFI surveillance in Sierra Leone. Using a mixed method approach, we retrospectively reviewed passive data collected during a 2021 immunization campaign, and conducted semi-structured, interviews with vaccinators, district AEFI focal persons, and key stakeholders at the national Expanded Program on Immunization and the National Medicines Regulatory Authority. AEFI were categorized using the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms (PTs) and System Organ Class (SOC). Outcomes were stratified as recovered or not, with preventability and causality assessed using the Schumock and Thornton and World Health Organization (WHO) algorithms, respectively. A total of 528 suspected AEFI were documented, predominantly affecting children aged 28 days to 23 months (63.3%). Most reported AEFI were administration site conditions and general disorders, with pyrexia being the predominant PT. Of 80 serious cases, 78 recovered, with 74 having an inconsistent causal relationship with the vaccine. Most serious cases (78) were deemed non-preventable, with only two being probably preventable. AEFI reporting was not routinely carried out across the group of people interviewed. AEFI reporting was not consistently performed, with discrepancies in defining reportable events and confusion over responsibility. Challenges with the open data kit (ODK) platform were noted, along with perceived inadequacies in training. While the nOPV2 is relatively new, the majority of AEFI were not serious, and most serious cases were not causally linked to the vaccine. Participants exhibited variations in experience and awareness of AEFI reporting.