D-dimers may be elevated after surgery. However, the kinetics of postoperative D-dimers remains unknown hampering the use of D-dimer testing in surgical patients with suspected venous thromboembolism. D-dimer levels were prospectively measured in 154 patients after general surgery at predefined time points (kinetics were determined in an initial cohort of 108 patients; for validation, these findings were applied to a second cohort of 46 patients). Clinical factors influencing the peak of D-dimers were analyzed using multivariate regression. Surgical operations were stratified based on severity (type I: not entering abdominal cavity; type II: intraabdominal; type III: retroperitoneal/liver surgery). D-dimer levels increased postoperatively reaching a peak on day 7. After type I surgery, peak D-dimer levels did not exceed normal range (300 ng/ml, 100-500). After type II procedures, peak D-dimer level was 1500 ng/ml (200-7800) and returned to normal values after 25 days (+/-14). Peak level was 4000 ng/ml (500-14 400) after type III surgery normalizing within 38 days (+/-11). Clearance of D-dimer was exponential after having reached the peak with 6.0% per day (95% confidence interval 4.8-7.1%). By this clearance, D-dimer values could be adequately predicted in the validation cohort after day 7 (r2 = 0.63). Peak D-dimer levels were independently influenced by the type of surgery (P < 0.001), the operation time (P < 0.001) and by preoperatively elevated D-dimer levels (P < 0.001). Based on this data, duration of postoperative D-dimer elevation after abdominal surgery is predictable. This study indicates for the first time when D-dimers may be used again in the diagnostic algorithm for venous thromboembolism exclusion after surgery in patients with low or moderate clinical probability.