Introduction: Although the risk of urethral trauma while treating bladder stones is worrisome, evidence about the best treatment approach is scarce. The aim of this study is to compare the safety and efficacy of transurethral cystolithotomy and percutaneous suprapubic cystolithotomy in adults´ bladder lithiasis treatment. Methods: We retrospectively evaluated 120 patients (January 2012 to December 2017) who were surgically treated for bladder lithiasis with percutaneous suprapubic cystolithotomy (n= 20) and transurethral cystolithotomy (n= 100). Age, gender, calculi size, surgery duration, hospital stay, post-operative infections, haematuria, pain and urethral strictures were evaluated. Previous diagnosis of benign prostate hyperplasia and urethral strictures were also considered. Results: Both groups were homogeneous according to the pre-operative variables evaluated, including calculi dimensions and simultaneous diagnosis. Median surgery time in percutaneous suprapubic cystolithotomy and transurethral cystolithotomy were 65 and 58 minutes, respectively (p= 0.043). Pain and haematuria were similar in both groups. Median hospital stay was 2.0 days in both groups. Median follow-up time was 13 months. In the transurethral cystolithotomy, three patients (3%) developed urethral stricture while none of the patients treated with PSC developed urethral strictures during the follow-up (p= 0.435). Discussion: Percutaneous suprapubic cystolithotomy theoretically offers an advantage over transurethral cystolithotomy in terms of urethral trauma, although we did not observe a significant difference. However, it deserves to be considered, especially in patients with known urethral strictures that may hinder transurethral access. Further prospective studies with more patients may however confirm these theoretical advantages.