Aims: To identify subgroups of patients with renal stones ≥20 mm that are more suitable for extracorporeal shock wave lithotripsy (ESWL) monotherapy. Methods: A total of 376 patients with renal stones ≥20 mm underwent monotherapy with ESWL. The treatment outcome was evaluated after 3 months of follow-up. A stone-free status or fragmentation of stones to 4 mm or smaller was considered efficacious. Results: At 3 months after treatment, the overall stone-free rate was 64.4%, and the efficacy rate was 70.7%. The efficacy rate was 89.4% for patients with a residual stone surface area ≤50% of baseline after the first ESWL, while the efficacy rate was 32.4% for other patients. The efficacy was 92.2% for stones ≤400 mm2 and those with lower radiodensity, as determined by a plain (KUB) film. Conclusions: For renal stones with a surface area ≤400 mm2 and a radiodensity equal to or less than that of the 12th rib as determined by a KUB film, ESWL may be considered the first line of treatment, even for stones with a diameter ≥20 mm. For large stones requiring repeat treatments, the surface area of the residual stones after the first ESWL is a predictor of the final treatment result.