Introduction: Zinner syndrome (ZS) is a rare congenital malformation (incidence: 214/100.000 patients), characterized by unilateral renal agenesis/dysplasia, seminal vesicle cysts and ipsilateral ductus deferens obstruction. ZS results from a defect in early embryogenesis in the distal part of the mesonephric duct. It is generally asymptomatic until the second decade of life; with the onset of sexual activity, non-specific symptoms such as perineal and scrotal pain may occur. Several studies show that around 45% of ZS patients are infertile. It’s usually diagnosed in symptomatic patients by transrectal or transabdominal ultrasound while abdominal-pelvic magnetic resonance imaging (MRI) confirms the diagnosis. Treatment depends on the patient's symptoms: conservative approach to the standard surgical treatment, transurethral resection of the ejaculatory duct (TURED). Materials and Methods: 4 patients (age 20-35 years old) referred to the Laboratory of Seminology–Sperm Bank “Loredana Gandini” with a diagnosis of symptomatic ZS to perform semen analysis and evaluate the possible impact of ZS on the semen quality before and after TURED. Hormone profile, semen analysis (according to WHO 2010), Direct SpermMar Test and Gelatin Agglutination Test (GAT) in serum and seminal plasma and analysis of seminal plasma fructose and acid phosphatase were performed. Results: 3/4 subjects showed seminal parameter values > 5° percentile pre-TURED; 1/4 had azoospermia after TURED. Direct and indirect test of ASA in serum and seminal plasma was positive in 3/4 after TURED and 1/4 who didn’t undergo surgery. 4/4 showed hormone profiles within range of references. Biochemical analysis of seminal fluid found elevated acid phosphatase values in 2/4 after TURED and 1/4 who didn’t undergo surgery. Discussion and Conclusion: To the best of our knowledge, this is the first study to evaluate serum and seminal plasma ASA in men with ZS. It is known that specific serum antibodies to human sperm occur in conditions that compromise the blood-testicular barrier or result in excessive sperm inoculation from the male genital tract due to 'leakage' or obstruction. ASA have been found in serum of patients with testicular trauma, vasectomy, genital infections, congenital absence of the vas deferens, cystic fibrosis and other acquired obstructions. As men with ZS have unilateral obstruction of the vas deferens, we investigated whether these men developed serum and plasma ASA. 3/4 subjects were examined only after surgery, and therefore we cannot say whether the presence of ASA is due to typical obstruction of the spermatic duct in ZS, or to the alteration of the blood-testicular barrier caused by the inflammation or complications of surgery. The finding of ASA in combination with an elevated acid phosphatase and a low fructose level is suggestive of obstructive azoospermia in 1/4 of cases. This is probably due to complications of TURED, and highlights the importance of preoperative semen cryopreservation. In 2/4 of the patients after TURED, no significant abnormalities were found in semen parameters. However, the presence of ASA could prevent fertilisation in vivo and therefore suggest to the clinician that the patient should be referred for artificial reproductive technologies (ART).