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Objective: Percutaneous nephrolithotomy (PCNL) is the minimally invasive procedure of choice for removing renal stones larger than 2 cm. This study has aimed to identify the different variables that might influence decrease of hemoglobin during the surgery performed in supine position., Material and Methods: A prospective, multicenter, observational study of supine PCNL, based on the Spanish Association of Urology database, was analyzed. The different preoperative and postoperative factors that might affect the decrease of hemoglobin were assessed: demographics and anthropometric data, comorbidities, size and location of the stones, anatomical variants and technical aspects of the procedure., Results: From September 2008 to December 2012, 397 supine PCNL procedures performed in 15 Spanish centers were registered. Mean hemoglobin decrease was 2.3±1.5 g/dl and overall blood transfusion rate was 5.5%. No statistically significant differences were found between genders, body mass index (BMI) and age in terms of blood loss. There were also no differences between patients with cardiovascular, hypertensive, diabetic and anticoagulant treatment background. Blood loss was not significantly influenced by stone size and location. Technical aspects of the procedure as operative time (> 120 min ≤), access to the pelvi-caliceal system (ultrasound, fluoroscopy), percutaneous tract dilation technique (Alken, balloon or Amplatz) or placement of nephrostomy (tube versus tubeless) were not associated with differences in pre-op/post-op hemoglobin. Only multiple percutaneous tracts (≥2) and middle calix access were statistically significantly (P=.03 and P=.01) related with less blood loss., Conclusions: PCNL in supine position is a minimally invasive procedure for removal of large (≥2 cm) and multiple renal stones, with a low incidence of blood loss and minimal transfusion rate. Multiple percutaneous tracts and middle calix puncture were the only statistically significant variables associated with decrease in hemoglobin levels., (Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.)