Background/Objectives: Recent trends show a rising incidence of venous thromboembolism (VTE) that does not correlate with increased mortality; however, population aging and the proliferation of comorbidities are fundamentally reshaping the VTE patient landscape. The aim of this study is to evaluate potential differences in clinical characteristics, comorbidities, and survival rates between patients diagnosed with pulmonary embolism (PE) during the pre-pandemic period (2018−2019) and those diagnosed during the pandemic era (2020−2022). Additionally, as a secondary objective, we analyze the clinical profiles, risk factors, and survival outcomes of patients with and without COVID-19 infection during the 2020−2022 period. Methods: A retrospective observational study was conducted to analyse survival and comorbidities in patients admitted for PE at the Hospital Central de la Defensa ‘Gómez Ulla’ between 2018 and 2022, comparing two periods (2018−2019 and 2020−2022). In addition, a sub-analysis was performed within the second period group comparing patients with and without COVID-19. Results: It was observed that the majority of patients in the first period were men, while in the second period, 55% were women. With regard to comorbidity and risk factors, thrombophilia and dementia were more prevalent in the first period, while immobilization, a history of asthma, autoimmune diseases and infections were more prevalent in the second period. No differences were found with regard to mortality. Conclusions: Significant differences were observed between the two periods of the study with regard to age, gender, and some comorbidities. Patients with COVID-19 showed a greater tendency toward immobilization and a higher prescription of thromboprophylaxis during hospitalisation.