Primary effort thrombosis is a noniatrogenic deep vein thrombosis of the upper extremity. The incidence of this condition is 1 to 2 in 100,000 per year. The risk factors and typical patient population differ from other thrombotic events. Patients with primary effort thrombosis are typically young, athletic, and lack comorbidities. Due to its low incidence and unique risk factors, primary effort thrombosis often is misdiagnosed as a musculoskeletal injury. However, early recognition, initial testing with Doppler ultrasound, and immediate referral to a vascular center is essential to achieve optimal outcomes. This article reviews risk factors, pathogenesis, presentation, diagnosis, and acute management of primary effort thrombosis for primary care providers.