Retained hemothorax is a challenging clinical entity characterised by the accumulation of blood within the pleural cavity following chest trauma or surgery. In recent years, intrapleural streptokinase has emerged as a potential therapeutic option for managing retained hemothorax, offering a less invasive alternative to surgical interventions. However, limited data are available on the efficacy of this treatment modality in the Pakistani population. Objective: This study aimed to evaluate the effectiveness and safety of intrapleural streptokinase in resolving retained hemothorax among patients in Pakistan. Methods: A prospective observational study was conducted at a Rawalpindi Teaching Hospital in Pakistan from January 2022 to July 2023. One hundred patients meeting the inclusion criteria were enrolled in the study. Baseline demographic and clinical data were recorded, and intrapleural streptokinase therapy was administered according to standard protocols. Response to treatment was assessed through regular clinical examinations and radiological imaging over a predetermined duration. Descriptive statistics were used to summarise baseline characteristics, and inferential statistics, such as chi-square tests or t-tests, were utilised to compare outcomes between subgroups. Results: Of the 100 patients treated with intrapleural streptokinase therapy, 85% achieved successful resolution of retained hemothorax, as evidenced by complete drainage of blood from the pleural cavity and radiological confirmation of lung re-expansion. A subset of patients who did not respond to therapy required additional surgical interventions. Minor complications were observed in 10% of the study population. Conclusion: Intrapleural streptokinase therapy demonstrated promising outcomes in resolving retained hemothorax among patients in Pakistan. Despite the need for additional surgical interventions in some cases, this treatment modality's overall efficacy and safety profile supports its consideration as a first-line therapy for retained hemothorax in resource-limited settings.