There has been continuing controversy regarding multiple tracts in a percutaneous nephrolithotomy (PCNL) session that may bring more complications, especially severe bleeding need for transfusion, even nephrectomy. Little tracts may bring less trauma to renal parenchyma than standard PCNL tracts. We carried minimally invasive PCNL (MPCNL) in treating staghorn calculi with multiple 16Fr percutaneous tracts in a single session, in an attempt to get high stone free with little trauma, and compared the morbidity of standard PCNL procedures in a prospective trial. A total of 54 consecutive patients with staghorn calculi were prospectively randomized for MPCNL (29) and PCNL (25). The size and location of stone, operative parameters, number of tracts, stone-free rate, operating time, hospital stay and complications were analyzed. In MPCNL group, a total of 67 percutaneous tracts were established in 29 renal units, while 28 tracts in 25 renal units in PCNL group. Compared to PCNL, MPCNL was associated with higher clearance rate (89.7 vs. 68%, p = 0.049), less chance need for adjunctive procedure of SWL or second-look PCNL (24.1 vs. 60%, p = 0.007), while a similar complication rate (37.9 vs. 52%, p = 0.300). In conclusion, with the development of instruments and increased experience, judiciously made multiple percutaneous tracts in a single session of MPCNL for treating staghorn calculi were safe, feasible and efficient with an acceptable morbidity.