The effects of treatment modalities such as retrograde intrarenal surgery (RIRS) and shock wave lithotripsy (SWL) on health-related quality of life (HRQoL) were determined in patients with renal stones between 10 and 20 mm. A total of 120 patients were included in the study and prospectively randomized to RIRS or SWL group. A total of 39 patients experienced treatment failure and finally 81 patients (45 patients in the RIRS group, 36 patients in the SWL group) were analyzed for HRQoL. SF-36 survey was used to determine HRQoL pre-operatively, post-operative day 1 and 1 month. The patient and stone characteristics such as age, gender, stone size, grade of hydronephrosis and body mass index were similar between the two groups. At post-operative day 1, the RIRS group was associated with lower scores of role functioning/physical (p = 0.008), role functioning/emotional (p = 0.047) energy/fatigue (p = 0.011), social functioning (p = 0.003) and pain (p = 0.003) when compared to the SWL group. At post-operative 1 month, only pain and emotional well-being scores (p = 0.012 andp = 0.011, respectively) in the RIRS group were statistically lower according to the SWL group. In our study, patients in the SWL group showed more favorable HRQoL scores when compared to the patients in the RIRS group in short-term follow-up.