A patient with acute abdominal pain requires rapid evaluation. In these patients, it is very important to distinguish between surgical and nonsurgical pathology. Our aim was to compare the accuracy of the leukocyte count and D-dimer test in the diagnosis of acute abdomen. In this prospective study, 225 patients admitted to the emergency unit due to nontraumatic acute abdomen between June 2006 and November 2007 were evaluated. The patients were divided into two groups: Group 1 patients who needed immediate laparotomy and Group 2 patients who did not. Age, gender, leukocyte count, D-dimer level, causes of acute abdominal pain, and operative findings were investigated. P values of <0.05 were considered statistically significant. There was a positive correlation between the plasma D-dimer level and leukocyte count. D-dimer acted similarly to the leukocyte count in emergency abdominal conditions. The area under the receiver operating characteristic curve was statistically higher with the D-dimer test (p<0.0001). Additionally, in patients needing immediate laparotomy, the sensitivity of the D-dimer test was 95.7% versus 74.8% for leukocyte counts. In a patient with acute abdomen, D-dimer test may be a strong alternative or an adjuvant to the leukocyte count.