This study assesses the experiences of parents/caregivers regarding the refusal to childhood immunization. A cross-sectional study was conducted among the parents/caregivers of children under two years old from January 2019 to June 2019 who were residents of either Pathan Colony or Orangi Town, Karachi. In this study, the data collectors targeted parents/caregivers of 440 households who showed a refusal mark “R” in the Expanded Program of Immunization (EPI) H-chalking system. These households were approached using a 30 × 7 multistage-stratified-cluster random sampling technique and were interviewed using a structured questionnaire. The study sample produced two different types of refusals: true refusal (absence) and potential refusal (presence), based on the absence and presence of a vaccination card at the time of the survey. Multivariate logistic regression was used to analyze the data using Jamovi (V-1.6.13). A total of 230 households consented to participate in this study, of which 141 (61.3%) represented true refusals, while 89 (38.7%) represented potential refusals. More than half of the participants from both groups complained about fever and pain at the injection site following immunization. The use of alternative medicines and a history of adverse events following immunization (AEFI) were associated with increasing the odds of immunization refusals by four-to-five fold. However, advanced paternal age, a long distance to the clinic, a lack of trust in government, and the influence of community/religious leaders were associated with lower immunization refusal odds. Thus, an unawareness about self-limiting vaccine-related adverse events, the use of alternative medicines, and an increased concern about the safety and efficacy of vaccines were found to be barriers to immunization, which can be improved by increasing public awareness through media campaigns and policy reform.