Introduction: The indication to treat varicocele remains challenging in male factor infertility (MFI) patients. The presence of semen abnormalities and the absence of further possible causes of MFI usually guide the indication to treat a varicocele. Some markers of semen quality, such as the sperm DNA fragmentation index (SDF), might play a role in this setting. We aimed to assess the proportion of patients with pathological SDF in a cohort of white-European primary infertile men with varicocele. Methods: Complete clinical and sociodemographic data, including semen analysis and serum hormones, were retrospectively collected from 1021 patients seeking medical help for primary infertility and concomitant varicocele without evidence of any other cause for the infertility. Infertility and semen analyses were defined according to the WHO 2010. SDF was considered as pathological for values >30%, according to SCSA. Clinical grades of varicocele were classified according to WHO recommendations. Hence, patients were stratified in those with/without concomitant semen abnormalities (any). Descriptive statistic was used for assessing differences in baseline characteristics. Multivariable regression analysis evaluated the association between the severity of varicocele and SDF. Results: Of 1021 men, 119 (11.6%) did not present any semen abnormality, while 902 (88.4%) had at least one semen abnormality, of which 539 (59.8%) had oligozoospermia, 39 (4.3%) azoospermia, 670 (74.3%) asthenozoospermia and 670 (74.3%) teratozoospermia. There was no difference in median age at presentation [ [23.9 years (22.8-25.8) for those without semen abnormalities and 24.6 years (22.9-26.6) for those with semen abnormalities (any)], number of comorbidities (CCI=2 in 44 [37.0%] and 272 [30.2%] patients, respectively) and BMI [23.9 (22.7-25.8) and 24.6 (22.8-26.6) kg/m2, respectively]. SDF was 23.7 (13.4-34.56) vs. 33.3 (21.7-50.0) (p < 0.001) for those without and with semen abnormalities, respectively. Interestingly there were 68 patients (57.1%) with altered SDF among those with non-altered seminal analysis vs. 377 patients (41.8%) among those with altered seminal analysis (p < 0.002). At multivariable analysis altered SDF was not associated with higher varicocele grades. Conclusions: Almost one out of two patients with varicoceles, no other known causes of infertility and no macroscopic semen abnormalities has high SDF. SDF is not associated with the grade of varicoceles but might per se still represent and indication for treatment. SOURCE OF Funding: None