Percutaneous nephrolitholapaxy (PCNL) with modern stone disintegration technologies is the treatment of choice for patients with extensive stone burden or stones refractory to extracorporeal shock wave lithotripsy. However, little is known about factors predicting unfavourable outcome in terms of perioperative complications, residual stone burden or prolonged hospitalization. The aim of this study was to evaluate preoperative, patient- and stone-related parameters that might influence the perioperative course and short-term clinical outcomes. In a prospective study, age, sex, body mass index (BMI), bidimensional size, side, pre-existent urinary tract infection, pre-existent hydronephrosis and previous kidney surgery were used as independent variables in both univariate and multiple regression models in 109 PCNL patients in order to predict the partition of patients rendered stone free at hospital discharge, duration of surgery, length of inpatient hospital stay and the occurrence of major complications. Univariate and multiple regression analysis revealed that stone size was the only factor influencing duration of surgery (P < 0.001) and hospitalization (P = 0.02), but had no predictive potential for major complications. Univariate analysis showed a trend towards longer inpatient hospital stay and clinically relevant residuals in patients with lower BMI (P = 0.05 and 0.06); however, after controlling for the other confounding variables, this was only reproducible for residual stone burden. The other patient- and stone-related factors did not adversely affect the outcome measures. In our patient sample treated with PCNL by LithoClast Master/Ultra we found evidence that large stone burden is a prognostic factor predicting longer surgery and prolonged hospitalization. In addition, patients with lower BMIs might be at higher risk of not being stone free at hospital discharge accompanied by prolonged inpatient treatment.