Objective: To evaluate safety and efficacy of trigone-involved Botox injections in comparison with trigone-sparing injections in refractory idiopathic overactive bladder (OAB). Materials and Methods: One hundred and three patients randomly received a 100-IU intradetrusal injection of Botox either sparing the trigone (52 patients) or involving the trigone (51 patients). Patients were prospectively evaluated at 1, 3, and 6 months. Efficacy was evaluated by 3-day voiding diaries, OAB symptom score (OABSS), and pressure flow study. Any complications were recorded. An ascending cystogram was done at 3 months for detection of vesicoureteral reflux. Urinary tract infection (UTI) was estimated on urine culture basis. Primary outcome was the difference of total OABSS at 3 months. Results: The mean age ± SD was 34.3 ± 10 years (range 18-59 years). There was a reduction of episodes of all components of OAB in both groups in comparison with baseline by the end of the study but without significant difference between both groups. The trigonal-sparing group had less score of frequency compared with the trigonal-involved group throughout the study period (P < .05). There was no difference in OABSS at 3 months (1.5 ± 0.4 vs 1.6 ± 0.3, P .875). Two patients in the trigonal-involved group out of 51 (3.9%) were in need of clean intermittent catheterization because of voiding difficulty and a postvoid residual > 200 mL. There was a higher rate of UTI in the trigonal-involved group ranging from 5.6% up to 11.7% at each follow-up visit. No patient had reflux. Conclusion: Trigone injections are not superior to trigone-sparing injections. On the contrary, the incidence of UTI and voiding difficulty were higher. The concept of reflux induced by trigonal injection has not been proven.