To present a combined endourologic approach to treat bladder calculi consisting of simultaneous percutaneous suprapubic and transurethral cystolithotripsy. We report on a series of 12 consecutive patients with bladder stone burdens of 40 mm or greater. Percutaneous 30F access was obtained under cystoscopic control. Fragmentation and stone removal were performed simultaneously by two urologists using a Swiss lithoclast, holmium laser, and/or ultrasound lithotriptor through both percutaneous and transurethral routes. Suprapubic and transurethral catheters were placed postoperatively. Twelve patients with a median age of 66 years (range 33 to 80) were treated by simultaneous percutaneous suprapubic and transurethral cystolithotripsy. Six underwent transurethral resection of the prostate at the completion of stone clearance. The median stone size was 60 mm (range 40 to 80), and the median lithotripsy time was 56 minutes (range 45 to 70). The median postoperative hospitalization was 2.7 days (range 2 to 5), and complete stone clearance was achieved in all cases. One patient, who underwent concomitant transurethral resection of the prostate, developed urinary retention 1 week postoperatively and was successfully treated by temporary transurethral catheterization. One patient with a positive urine culture preoperatively developed fever on the first postoperative day and was treated with intravenous antibiotics according to the antibiogram results for 5 days. No other complications had occurred after a median follow-up of 10 months (range 3 to 15). Simultaneous percutaneous suprapubic and transurethral cystolithotripsy appears to be a safe approach for the management of large bladder calculi and may shorten the total fragmentation time. It can be combined with transurethral resection of the prostate without prolonging hospitalization. The simultaneous use of two modalities of stone fragmentation represents an effective and minimally invasive way of treating large bladder calculi.