The aim of this study was to evaluate the outcome of staged single-tract minimally invasive percutaneous nephrolithotomy (MPCNL) and flexible ureteroscopy as a minimally invasive option in the treatment of staghorn stone in patients with a solitary kidney. A total of 24 patients with staghorn stone in a solitary kidney were treated with single-tract MPCNL and flexible ureteroscopy by a single surgeon. All the patients underwent single-tract MPCNL through a 20 F tract and had most of the intrarenal calculi removed at the first stage. The second stage of retrograde flexible ureteroscopy was performed 3-5 days later, after the drainage was cleared. The preoperative patient, characteristics, stone size, operative time, renal functional status and postoperative outcomes were then evaluated. Sixteen patients were partial staghorn (66.7 %), and other eight were complete staghorn (33.3 %). The overall stone-free rate was 83.3 % after the second-stage procedures, and only four patients had significant residue. The hemoglobin drop ranged from 1.1 to 3.7 g/dl, and three patients required blood transfusion. The mean serum creatinine value was 1.7 ± 0.5 mg/dl before surgery and 1.3 ± 0.4 mg/dl at the end of the follow-up period with statistical significance (P < 0.05). None of the patients had increased serum creatinine, and needed dialysis at the end of the follow-up period. Staged single-tract MPCNL and flexible ureteroscopy are safe and effective for the management of staghorn stone in patients with a solitary kidney and even in patients with impaired renal functions.