Varicocele, the most common cause of male infertility, is defined as abnormal dilation of the pampiniform plexus. Although different mechanisms have been proposed to explain the pathophysiology of infertility caused by varicocele, it is still open to debate. Previous studies have demonstrated the effect of insulin-like growth factor-I (IGF-I) on semen quality in animals and humans, but there are no studies on the probable role of seminal IGF-I in the pathophysiology of infertility among patients with clinical varicocele. We therefore aimed to examine the seminal IGF-I concentration in 49 patients with varicocele and primary infertility before and after varicocelectomy and compare the results with those of 50 healthy fertile men (in the control group). Mean seminal IGF-I level of patients before varicocelectomy (93.7 ± 67.2 ng/mL) was significantly different (P < 0.001) from that following varicocelectomy (58 ± 35.1 ng/mL) and from that of the controls (57.6 ± 22.1 ng/mL). However, mean seminal IGF-I levels of patients after varicocelectomy and the controls were not significantly different. Seminal IGF-I level was not correlated with grade and side of varicocele, and semen quality. We conclude that locally secreted IGF-I in the semen may be involved in the pathophysiology of infertility in patients with varicocele or semen.