Percutaneous nephrolithotomy has become the preferred treatment for large and/or complex renal and proximal ureteral calculi. The objective of this chapter is to evaluate the efficacy and safety of tubeless percutaneous nephrolithotomy. We analyzed published studies from the last 15 years and reviewed the current literature for indications, outcomes, and complications. Tubeless percutaneous nephrolithotomy is demonstrated to be an effective and safe procedure for treatment of renal stones with the advantages of shorter hospital stay, lower analgesic requirements, lower costs, lower urinary leakage and with similar complication rates compared to the standard approach. Stone-free rates as high as 89% have been reported. Safety has also been demonstrated in children, obese patients, and bilateral procedures. In patients with intraoperative complications such as severe bleeding, gross perforation of the collecting system and in patients with multiple access tracts or the need for a staged procedure, nephrostomy tube placement should be strongly considered.