Nowadays, most studies of tuberculous epididymo-orchitis (TBEO) are case reports or small sample cohort series. Our study is aimed to present the largest series of TBEO with our management experiences and long-term follow-up outcomes.Patients diagnosed with TBEO after surgical procedures at Department of Urology, West China Hospital from 2008 to 2019 were included. All clinical features, auxiliary examination results, treatment and histopathological findings were extracted if available.Eighty-one patients (mean age 50.77 ± 16.1 years) were included. Scrotal swelling (N = 47, 58.0%) and pain (N = 29, 35.8%) were the most common presenting complaint. Pyuria and microscopic hematuria were observed in twenty-two (27.2%) and eight patients (9.9%), respectively. Urine acid fast bacilli cultures were available in 16 patients and all were negative. The mean duration between the onset of symptoms and the definite diagnosis was 6.42 ± 7.0 months. TBEO was considered in 30 (37.0%), tumors in 28 (34.6%) and nonspecific bacterial epididymo-orchitis in 23 (28.4%) patients. All patients received triple therapy of chemotherapy-surgery-pharmacotherapy and definite diagnosis was confirmed through histopathology of surgical specimens. Fifty-five patients were followed up regularly (mean follow-up 82.35 ± 36.6 months). One patient (1.2%) died from liver cirrhosis and no recurrence was observed. Postoperative complications included erectile dysfunction in 4 patients (4.9%), premature ejaculation in 5 patients (6.2%) and sterility in 7 patients (8.6%).We recommend patients with advanced TBEO to receive triple therapy of chemotherapy-surgery-pharmacotherapy. Physicians should pay more attention to patients' sexual function and fertility during follow up after treatment completed.© 2021. The Author(s).