Purpose: To evaluate the use of spinal anesthesia by reducing anesthetic agent dose to provide better analgesia with minimal side effects without sacrificing the outpatient setting for prostate biopsy. In this study, efficacy and tolerability of selective low-dose spinal anesthesia versus intrarectal local anesthesia (IRLA) plus periprostatic nerve blockade (PPNB) were compared. Methods: Between September 2012 and April 2013, 100 patients, aged 40 to 80 years, prostate-specific antigen (PSA) ≥4 ng/mL, abnormal digital rectal examinations, and enrolled for biopsy were included in the present study. Ensuring double blindness, pain was assessed using the visual analog scale (VAS). Anal sphincter relaxation, patient satisfaction with the anesthesia technique, and motor response were evaluated. Results: Differences between the two groups, considering age, American Society of Anesthesiologist score, total PSA, prostate volume, anesthesia duration, and cancer presence, were not statistically significant. Pain experienced during probe insertion, biopsy, and 30 minutes after biopsy was significantly lower in the low-dose spinal anesthesia group (P < 0.0001). Anal sphincter relaxation degree was significantly higher in the spinal group (P < 0.001). Patient procedure-related overall satisfaction level was significantly higher in the spinal anesthesia group (P < 0.001). In the spinal anesthesia group, no motor blockade was observed. Between the two groups, no statistically significant difference was seen with regard to complications (P > 0.05). Conclusion: Selective low-dose spinal anesthesia provides better pain relief than PPNB plus IRLA without sacrificing the day case setting in ambulatory practice. It is also associated with high patient satisfaction and willingness for a repeated biopsy without differences in procedure duration, tolerance, and complications.