Risedronate 5 mg daily is approved by the Food and Drug Administration to treat Postmenopausal osteoporosis. Gastrointestinal (GI) symptoms are common with daily bisphosphonates, but recent studies show that once weekly treatment may be better tolerated. Risedronate 30 mg is approved to treat Paget's disease of bone. In this retrospective study, we assessed the GI tolerability of 30 mg of risedronate once weekly and evaluated the effect on bone mineral density (BMD) in a subset of women. Review of patients treated in our osteoporosis clinic identified 150 postmenopausal women with low BMD treated with 30 mg of risedronate once weekly, between February 1998 and March 2001. Baseline GI symptoms or previous intolerance of bisphosphonates was present in 32 patients. An additional antiresorptive treatment was continued with risedronate in 50% of these patients (estrogen, raloxifene, or calcitonin). Risedronate 30 mg was taken once weekly with vitamin D 400 in daily and 1200 mg of calcium daily. Patient age ranged from 46 to 86 yr. Baseline and follow-up BMD data were available in 36 patients. Of the 32 patients with baseline GI symptoms or previous intolerance of a bisphosphonate, 1 developed GI symptoms. In those patients with baseline and follow-up BMD results (n = 36), BMD increased 1.9% (p = 0.02) at the trochanter and 2.1% (p = 0.001) at the total hip. In conclusion 30 mg of risedronate once weekly increased BMD at the trochanter and total hip (p < 0.05). This dosage was well tolerated with a low incidence of GI side effects.