The aim of the present study was to assess the safety and implementation of a diagnostic strategy in hospitalised patients with suspected acute pulmonary embolism (PE). A diagnostic strategy was established and implemented in a general hospital. A retrospective cohort study, including 400 consecutive in-patients, was performed in order to assess the appropriateness of the diagnostic management and the incidence of symptomatic venous thromboembolic events (VTE) during follow-up. PE was confirmed in 116 (29%) patients. The incremental value of adding compression ultrasonography (CUS) to multidetector-row computed tomography (MDCT) for the diagnosis of PE was 8.6%. PE was appropriately excluded in 169 (42%) patients due to a normal lung scan (n = 34), a negative MDCT providing an alternative diagnosis (n = 94), and a negative MDCT and CUS (n = 41). During follow-up, VTE occurred in 3.5% patients. The almost unique cause of inappropriate management was the absence of further work-up after a MDCT-negative result for PE providing no alternative diagnosis (n = 115). Inappropriate management was associated with a nonsignificant increased risk of VTE (7.2%). A frontline diagnostic work-up based on pulmonary multidetector-row computed tomography associated with a compression ultrasonography of the leg veins is effective and more sensitive than pulmonary multidetector-row computed tomography alone in ruling out pulmonary embolism.