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Garnet is a common U-bearing mineral in various magmatic and metamorphic rocks with a high U–Pb closure temperature (> 850 °C), rendering it a potentially valuable U–Pb geochronometer. However, a high U (> 10 ppm) garnet reference material that suits both quadrupole and/or multi-collector inductively coupled plasma mass spectrometry (ICP-MS) is yet to be established. This study evaluates a potential reference material for in situ garnet U–Pb analysis with anomalously high U content from the Prairie Lake alkaline complex, Canada. The PL57 garnet, occurring in a calcite ijolite, has high TiO2 (6.5–15.0 wt%, average 12.7 wt%) and Fe2O3 (17.1–21.3 wt%) contents and is a member of the andradite (26–66 mol.%)-morimotoite (18–41 mol.%)-schorlomite (16–35 mol.%) solid solution series. Four samples were dated by U–Pb ID-TIMS to assess reproducibility. Twelve TIMS analyses produced concordant, equivalent results. Garnet PL57 yielded a concordant age of 1156.2 ± 1.2 Ma (2σ, n = 10, MSWD = 1.0), based on ten analyses with two results discarded due to possible mineral inclusions (if included, the concordia age is 1156.6 ± 1.8 Ma; n = 12, MSWD = 2.0). PL57 had 27–76 ppm (average 41 ppm) U with Th/U of 0.51–0.68 (average 0.63). The total common Pb content ranged from 0.4 to 3.9 pg (average 1.1 pg). Laser ablation coupled with ICP-MS and high angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) imaging provide direct evidence that U is incorporated and homogeneously distributed within the garnet lattice rather than as defects or pore spaces. Published garnet samples and standards were then tested by calibrating the Willsboro, Mali, Qicun, and Tonglvshan garnet against PL57, which gave accurate ages within the recommended values. Case studies of garnet from the Archean Musselwhite orogenic gold deposit in Canada and the Cenozoic Changanchong and Habo skarn deposits in China yield reliable ages. This suggests that PL57 is a robust U–Pb isotope reference material. The limited variations of U and Pb isotopic ratios, together with the high U concentration and extremely low initial common Pb, make PL57 an ideal calibration and monitor reference material for in situ measurements. [ABSTRACT FROM AUTHOR]