To find the most beneficial method, we assessed patient comfort and morbidity rates during prostate biopsy procedures performed using periprostatic nerve blockade, unilateral pudendal nerve blockade, intrarectal lidocaine gel, and a combination of periprostatic nerve blockade and intrarectal lidocaine gel. A total of 159 patients were included in this study. Pain evaluation results were retrospectively assessed and retrieved from the patient charts. Patients in group 1 (n = 64) received no anesthesia, group 2 (n = 34) received periprostatic nerve blockade, group 3 (n = 26) received unilateral pudendal nerve blockade, group 4 (n = 20) received intrarectal lidocaine gel, and group 5 (n = 15) received a combination of periprostatic nerve blockade and intrarectal lidocaine gel. A visual analog scale (VAS) was used for pain evaluations. According to pain scores (VAS) during probe insertion, only group 2 did not show a statistically significant difference (P > 0.05), while the other groups were found to be significantly different when compared to group 1. Groups 2, 3, and 5 were found to be significantly different when compared to group 1 according to pain scores (VAS) during insertion of needles. Groups 3 and 5 displayed statistically significant differences when compared to group 1 as regards pain scores during both the insertion of the probe and biopsy. Our data suggests that using either a combination of intrarectal lidocaine gel and periprostatic block or solely unilateral pudendal nerve block for prostate biopsy procedures provides efficient patient comfort by reducing pain both during probe insertion and needle passing through the prostate gland.