OBJECTIVE To compare the metabolic profile of patients who form mixed calcium oxalate (CaOx)/uric acid (UA) stones to those of pure CaOx and pure UA stone formers. METHODS We performed a retrospective review of 232 patients, with both stone composition analysis and 24-hour urine collection, seen between March 2002 and April 2012. Analysis of 24-hour urine constituents across the 3 stone groups (pure UA, pure CaOx, and mixed CaOx/UA) was performed using univariate analysis of variance and multivariate linear regression models adjusting for clinical and demographic factors and 24-hour urine collection elements. RESULTS A total of 27 patients (11.6%) had mixed CaOx/UA, 122 (52.6%) had pure CaOx, and 83 (35.8%) had pure UA calculi. Univariate analysis demonstrated significant differences between mixed CaOx/UA patients and pure CaOx patients for urine pH (mixed, 5.63 ± 0.49 vs pure, CaOx 5.93 ± 0.51; P = .009) and supersaturation (SS) UA (mixed, 1.84 ± 1.09 vs pure, CaOx 1.26 ± 0.93; P = .01), and a significant difference between mixed CaOx/UA patients and pure UA patients for SS CaOx (mixed, 7.18 ± 4.23 vs pure, UA 4.90 ± 2.96; P = .005). Multivariate analysis demonstrated that mixed CaOx/UA patients had no significant difference in SS CaOx as compared with pure CaOx patients (difference, -0.27; P = .66), whereas at the same time had no significant difference in SS UA as compared with pure UA patients (-0.07; P = .69). CONCLUSIONS The metabolic profile of patients who form mixed CaOx/UA stones demonstrates abnormalities that promote both CaOx and UA stone formation. Dietary and medical management for this group of patients should address treatment of both defects.