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Introduction Microdenervation of the spermatic cord (MDSC) has been demonstrated to be an effective treatment for men with intractable scrotal content pain. Aim This study evaluates the correlation between a positive response to a spermatic cord block with local anesthetic and the subsequent surgical outcome following MDSC. Main Outcome Measures Pre- and post-cord block pain and pre- and post-MDSC pain. Methods A retrospective review of 74 patients (77 testicular units) who underwent MDSC from 2006 to 2010 was performed. Pre- and post-spermatic cord block pain scores based on a 0–10 visual analog scale (VAS) were compared with pre- and post-MDSC pain scores. A positive response to the block was defined as greater than or equal to 50% temporary reduction of pain based on VAS. Results The average patient age was 42 years with a mean follow-up of 10 months. The mean duration of symptoms before surgery was 69 months. Mean pre-cord block pain score was 8 with an 89% average decrease in pain following the block. Mean post-MDSC pain score was 2 with an average decrease of 73%. The level of temporary improvement from the cord block appeared to be a useful predictor of sustained improvement with MDSC ( P = 0.05). Positive response to spermatic cord block was an independent predictor of MDSC response ( P = 0.03). Conclusions Men with chronic orchialgia who have a positive response to a spermatic cord block are likely to have durable and complete resolution of symptoms after undergoing MDSC. The amount of pain relief obtained after the cord block correlates with pain relief after undergoing a MDSC. Men with chronic orchialgia who desire surgical correction should undergo a preoperative spermatic cord block as part of their complete evaluation. The result of the cord block can help guide the practitioner and the patient toward definitive surgical management via MDSC. Benson JS, Abern MR, Larsen S, and Levine LA. Does a positive response to spermatic cord block predict response to microdenervation of the spermatic cord for chronic scrotal content pain? J Sex Med 2013;10:876–882.