OBJECTIVE. Periprosthetic bone cysts are a known finding after total ankle replacement (TAR). The significance of cysts is uncertain, but they may threaten the long-term survival of the implant. The aim of this prospective study was to evaluate the diagnostic accuracy of weight-bearing digital radiography compared with 3D weight-bearing multiplanar reconstructed (MPR) fluoroscopic imaging when diagnosing periprosthetic bone cysts in patients who have undergone TAR. SUBJECTS AND METHODS. Forty-two consecutive patients with a Scandinavian Total Ankle Replacement (STAR) were consecutively enrolled and underwent digital radiography and 3D MPR imaging in the same session. All 3D MPR images were interpreted in a blinded fashion, specifically with regard to the presence and extent of periprosthetic bone cysts. Cysts were measured in three planes whenever possible. Interrater and intrarater reliability was assessed by using Cohen kappa test, and comparisons between the two modalities were performed with the Wilcoxon signed-rank and McNemar tests. RESULTS. Significantly more cysts were detected on 3D MPR (74 vs 55) (p = 0.03), with the mean size of cysts detected by 3D MPR significantly larger than that of cysts diagnosed on digital radiography (1545 mm3 vs 253 mm3) (p < 0.0001). Statistical analysis based on the presence or absence of cysts in individual patients did not show a significant difference between 3D MPR and digital radiography (p = 0.23). CONCLUSION. The data imply that cysts are better detected and more accurately measured with 3D fluoroscopic MPR imaging compared with digital radiography, which under-estimates not only the presence but also the extent of periprosthetic cysts.