Multiply substituted isotopologues (or ‘clumped isotopes’) represent a novel stable isotope technique that offers a versatile and powerful geothermometer. Being able to extract reliable temperature information from any carbonate phase significantly improves the petroleum geologist’s ability to reconstruct the thermal history of petroleum basins, or to better constrain diagenetic transformations in reservoir units. There has been a recent increase in the number of laboratories running clumped isotopes, and our group has worked on applying clumped isotope to reservoir-relevant questions with the joint financial support of Qatar Petroleum, Shell, & the Qatar Science and Technology Park. The presentation will attempt to address the advantages as well as challenges of clumped isotopes based on experience gained over the past four years. The first priority of our research is calibrations to reservoir conditions. The current temperature calibrations go up to 50˚C and are thus below most reservoir temperatures. To overcome this we have developed a pressure-controlled rig for carbonate precipitation at temperatures up to 250˚C. Initial results suggest that the slope of the empirical calibration follows a theoretical slope determined by thermodynamic equilibrium, and thus that data agree with theoretical models. Furthermore, as most subsurface fluids are brines, we did a series of experiments comparing the clumped isotope signature of a low-salinity control precipitation batch with a second batch precipitated at the same experimental conditions but higher salinity. This was done to assess potential ‘salinity effects’ on clumped isotopes analogous to what was observed for δ18O, but initial results suggest that these effects are negligible. Finally, a series of multi-proxy case studies based on outcrop analogues in the Middle East where clumped isotopes were applied to fault-calcite, fracture-related dolomite and matrix dolomite form the basis of a ‘best practice’ workflow that helps maximize the information gained from clumped isotopes and avoid interpretational pitfalls. We conclude that in all of the cases we have studied, the carbonate clumped isotopes offer a robust dataset that significantly reduces uncertainty in the interpretation of the thermal history of carbonate phases. Temperature calibrations and potential subsurface-relevant effects on clumped isotopes are now being constrained, warranting the use of the technique for subsurface applications.