The age of the giant Uragen sandstone-hosted Pb-Zn deposit in the western margin of the Tarim Basin in Northwest China has long been questioned due to the general paucity of minerals unequivocally linked to Pb-Zn deposition that can be precisely dated using conventional radiogenic isotopic techniques. This paper describes the petrographic characteristics of Pb-Zn ores and presents the results of in situ calcite U-Pb analysis using laser ablation sector field inductively coupled plasma mass spectrometry (LA-ICP-MS) for this deposit. Calcite from the early, main and late ore-forming stages yielded low intercept ages of 11.80 +/- 0.4 Ma, 10.9 +/- 0.3 Ma and 10.6 +/- 0.2 Ma, respectively, which constrain the Uragen Pb-Zn mineralization to the Late Miocene. Combined with the existing isotopic ages in the region, these new ages lead us to propose that the Uragen deposit formed during two hydrothermal episodes. The first refers to the oil-gas migration that occurred during the Middle Eocene to Early Miocene, which may be associated with the India-Eurasia collision and subsequent activity of the Main Pamir Thrust. The second refers to the Pb-Zn mineralization that occurred in the Late Miocene, which may be associated with the activity of the foreland thrust fault belt of South Tianshan and the Pamir Frontal Thrust (PFT). This study demonstrates the potential of using LA-ICP-MS U-Pb dating on calcite to constrain the ages of sandstone -hosted Pb-Zn deposits.