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Abstract Background Diuretics have been associated with impaired response and refractoriness in gout, but whether this effect is still present with new urate-lowering drugs (ULD) and treat-to-target strategies is unknown. The aim of the present study was to assess the impact of the diuretics on the response to ULD in patients with gout. Methods This was a retrospective analysis of an inception cohort. Participants were classified according to the type of ULD prescribed. We analysed the maximal dose of ULD (primary outcome variable), serum urate (SU) reduction, and the achievement of different SU targets (6 mg/dL, 5 mg/dL, and 4 mg/dL), according to the type of ULD prescribed and use of diuretics (loop and/or thiazide). We adjusted for confounders using multiple linear regression analysis. Results We included 245 patients: 208 treated with allopurinol (66 on diuretics, 31.7%), 35 with febuxostat (19 on diuretics, 57.6%), and 2 with benzbromarone. Significantly fewer participants in the allopurinol plus diuretics subgroup achieved SU levels of less than 5 mg/dL, but we found no other significant differences in SU targets associated with diuretics. Regarding the maximum ULD dose, a simple linear regression suggested an inverse relationship with diuretics (beta = − 0.125, p = 0.073), but this did not hold in the multivariable analysis (beta = − 0.47, p = 0.833). There was no association with febuxostat (beta = − 0.116, p = 0.514). Conclusion Diuretics do not appear to have a significant impact on managing gout.