Abstract: Interviews were conducted with 515 individuals between the ages of 20 and 80 years to gather data on acetazolamide therapy and the occurrence of urolithiasis. One hundred forty-eight patients were treated with chronic oral acetazolamide therapy for one week to 348 months (mean 40.9 months). The overall occurrence of individuals developing one or more stones was significantly higher in the group treated with acetazolamide than in the group not treated with acetazolamide ( P = 0.01, logistic multiple regression). Twelve patients developed one or more stones during acetazolamide therapy (interval between the initiation of therapy and the occurrence of the first stone was one to 108 months, mean 14.4 months. The rate of individuals developing one or more stones per year during acetazolamide treatment was 11 times higher than the rate in the group not treated with acetazolamide. The rate of individuals developing one or more stones per year during acetazolamide treatment was 15 times higher than the rate in the acetazolamide group prior to the initiation of acetazolamide therapy. Nine of the 12 individuals (75%) who developed calculi during acetazolamide therapy did so within the first 12 months of treatment. Ten of these patients were maintained on acetazolamide therapy and five (50%) developed a second stone in one to 88 months (mean 29.2 months). Eight patients with a history of a single episode of idiopathic urolithiasis were treated subsequently with acetazolamide (mean duration of therapy 28.8 months) without developing a second stone. The results of this study support the clinical impression that chronic acetazolamide therapy is associated with an increased occurrence of urolithiasis.