Background: Pulmonary embolism (PE) is a life-threatening cardiovascular emergency associated with significant morbidity and mortality, particularly in intermediate- and high-risk presentations. Outcomes of PE vary widely across healthcare settings, influenced by patient characteristics, comorbidities, available diagnostic, proper management and therapeutic resources. Methods: We conducted a retrospective descriptive study in two tertiary referral hospitals in Yaoundé, Cameroon, including patients aged ?20 years admitted with confirmed intermediate- or high-risk PE between January 2015 and December 2020. Sociodemographic data, comorbidities, preclinical findings, treatment modalities, and in-hospital outcomes were extracted from medical records. The primary outcome was all-cause in-hospital mortality, while secondary outcomes included bleeding complications, recurrent PE, and length of hospital stay. Factors associated with mortality were assessed using univariate analysis. Results: Eighty-six patients were included, with a female predominance (62.8%) and a mean age of 52.5 ± 15.9 years. Hypertension (45.3%) and obesity (34.9%) were the most frequent comorbidities. The mean length of hospital stay was 8.8 ± 3.1 days. Overall, 80.2% of patients achieved complete clinical recovery. Anticoagulation with low molecular weight heparin was administered to 97.7% of patients, while systemic thrombolysis was used in only 14%. Minor bleeding complications occurred in 8.1% of patients, with no major or fatal bleeding events. One patient (1.2%) developed recurrent PE during hospitalization. The overall in-hospital mortality rate was 18.6%. Previous pulmonary embolism (OR 5.27; 95% CI 1.56–18.06; p = 0.007) and atrial fibrillation on electrocardiography (OR 15.92; 95% CI 1.87–336.16; p = 0.020) were significantly associated with mortality. Conclusion: The management of intermediate and high-risk PE relies almost exclusively on anticoagulation, with systemic thrombolysis used in a minority of cases in this setting. Intermediate- and high-risk pulmonary embolism is associated with substantial in-hospital mortality in this setting. Prior pulmonary embolism and atrial fibrillation emerged as important factors associated with poor outcomes, underscoring the need for careful risk assessment and optimized management of high-risk patients.