Introduction: The objective was to evaluate the effect of hydrochlorothiazide and alendronate on urine calcium and bone mineral density in calcium stone-forming patients. Material and Methods: A prospective, non-randomized, non-observational comparative study was performed; this study included 111 patients with recurrent calcium stones, divided into 3 groups according to the treatment received. Group 1: 36 patients were treated with alendronate, 70 mg/week; Group 2: 34 patients were treated with alendronate, 70 mg/week + hydrochlorothiazide, 50 mg/day; Group 3: 41 patients were treated with hydrochlorothiazide, 50 mg/day. All patients received recommendations on diet and fluid intake. Other variables of bone mineral density were studied and analyzed, including bone remodeling markers and urinary calcium before and after 2 years of treatment. The statistical analysis was performed using the SPSS 17.0 program, with a statistical significance of p < 0.05. Results: After 2 years of treatment, a significant difference was observed in the β-crosslaps and a bone mineral density improvement in Group 1, along with a decrease in urinary calcium. In Group 3, a statistically significant difference was found in urinary calcium and fasting calcium/creatinine ratio, as well as an improvement in bone mineral density after 2 years of medical treatment. In Group 2 patients treated with the combination, there was an improvement in bone mineral density and a decrease in the β-crosslaps marker similar to patients in Group 1, and a decrease in urinary calcium similar to those in Group 3. Conclusion: Combined alendronate + hydrochlorothiazide treatment offers the best results along with the improvement in bone mineral density and decrease in urine calcium in patients with recurrent calcium stones.