Four clinical decision rules (CDRs) (Wells score, Revised Geneva Score (RGS), simplified Wells score and simplified RGS) safely exclude pulmonary embolism (PE), when combined with a normal D-dimer test. Recently, an age-adjusted cut-off of the D-dimer (patient's age x 10 μg/l) safely increased the number of patients above 50 years in whom PE could safely be excluded. We validated the age-adjusted D-dimer test and assessed its performance in combination with the four CDRs in patients with suspected PE. A total of 414 consecutive patients with suspected PE who were older than 50 years were included. The proportion of patients in whom PE could be excluded with an 'unlikely' clinical probability combined with a normal age-adjusted D-dimer test was calculated and compared with the proportion using the conventional D-dimer cut-off. We assessed venous thromboembolism (VTE) failure rates during three months follow-up. In patients above 50 years, a normal age-adjusted D-dimer level in combination with an 'unlikely' CDR substantially increased the number of patients in whom PE could be safely excluded: from 13-14% to 19-22% in all CDRs similarly. In patients over 70 years, the number of exclusions was nearly four-fold higher, and the original Wells score excluded most patients, with an increase from 6% to 21% combined with the conventional and age-adjusted D-dimer cut-off, respectively. The number of VTE failures was also comparable in all CDRs. In conclusion, irrespective of which CDR is used, the age-adjusted D-dimer substantially increases the number of patients above 50 years in whom PE can be safely excluded.