The aim of this study was to evaluate the diagnostic value, in suspected infectious prostheses, of (99m)Tc-labeled hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) leukocyte scintigraphy interpreted with the addition of a semiquantitative analysis. By means of a retrospective review, we included a group of 78 consecutive patients with suspected hip or knee prosthesis infection. We performed 91 (99m)Tc-HMPAO-leukocyte scintigraphies and examined 95 localizations that were suspect. Images were acquired at 3 different time points after the injection of the labeled leukocytes: 50 min (early images), 4 h, and 24 h (late images). The scintigraphic examinations were independently evaluated by 3 observers; qualitative and semiquantitative analyses were performed. The final diagnosis of infection was based on surgical, histologic, and bacteriologic data and follow-up. On qualitative analysis, sensitivity, specificity, and accuracy were 80.4%-87%, 65.3%-71.4%, and 75.8%-77.9%, respectively. On semiquantitative analysis, sensitivity, specificity, and accuracy were 95.6%, 95.8%, and 95.8%, respectively. The analysis of 95% confidential intervals showed statistically significant differences in specificity and accuracy between semiquantitative and qualitative analyses. In those patients who underwent (99m)Tc-HMPAO-leukocyte scintigraphy for suspected hip or knee prosthesis infection, the addition of a semiquantitative evaluation to the qualitative analysis of early and late images leads to a significant improvement in both specificity and accuracy.