Introduction: The value of diagnostic strategies in patients with clinically suspected recurrent pulmonary embolism (PE) has not been established. The aim was to determine the safety of a simple diagnostic strategy using the Wells clinical decision rule (CDR), quantitative D-dimer testing and computed tomography pulmonary angiography (CTPA) in patients with clinically suspected acute recurrent PE. Materials and Methods: Multicenter clinical outcome study in 516 consecutive patients with clinically suspected acute recurrent PE without using anticoagulants. Results: An unlikely clinical probability (Wells rule 4 points or less) was found in 182 of 516 patients (35%), and the combination of an unlikely CDR-score and normal D-dimer result excluded PE in 88 of 516 patients (17%), without recurrent venous thromboembolism (VTE) during 3 month follow-up (0%; 95% CI 0.0-3.4%). CTPA was performed in all other patients and confirmed recurrent PE in 172 patients (overall prevalence of PE 33%) and excluded PE in the remaining 253 patients (49%). During follow-up, seven of these 253 patients returned with recurrent VTE (2.8%; 95% CI 1.2-5.5%), of which in one was fatal (0.4 %; 95 % CI 0.02-1.9%). The diagnostic algorithm was feasible in 98% of patients. Conclusions: A diagnostic algorithm consisting of a clinical decision rule, D-dimer test and CTPA is effective in the management of patients with clinically suspected acute recurrent PE. CTPA provides reasonable safety in excluding acute recurrent PE in patients with a likely clinical probability or an elevated D-dimer test for recurrent PE, with a low risk for fatal PE at follow-up.