Purpose: We performed a systemic review with meta-analysis to compare tubeless vs conventional percutaneous nephrolithotomy (PCNL) and assess the effectiveness and safety of this innovative procedure. Materials and Methods: A systematic review of PUBMED, EMBASE, LILACS, and Cochrane Library was performed to identify all randomized controlled trials (RCTs) that compared tubeless PCNL vs conventional PCNL. The analyzed outcomes were stone-free rate, pain assessment, analgesic medication requirements, operative time, hospitalization time, blood loss, and complications. Results: A total of 10 RCTs were identified that reported 621 patients. Seven studies analyzed stone-free rates. Meta-analysis of the data resulted in no difference between tubeless and conventional PCNL. Operative time, blood transfusion, hemoglobin drop and postoperative fever did not differ between the groups. Meta-analysis of length of hospitalization and prolonged urinary drainage was analyzed and favored the tubeless PCNL group. Conclusions: Tubeless PCNL is a safe and effective procedure with a stone clearance rate comparable to that of conventional PCNL. Tubeless PCNL presented a shorter hospital stay and less postoperative urinary leakage. Pain reduction and minimization of analgesic requirements also were demonstrated.