Objective: To study the pathogens distribution and drug resistance of nosocomial infection in patients with varicose veins of lower extremities (VVLE) after operation. Methods: The clinical data of 98 patients with postoperative nosocomial infection of VVLE who were treated in our hospital from February 2013 to February 2018 were analyzed retrospectively. The status of pathogen culture and isolation of postoperative nosocomial infection, as well as the influence of drug susceptibility test results on the degree of different antibiotic resistance were analyzed. Results: A total of 84 strains of pathogenic bacteria were detected in 98 patients with postoperative infection of VVLE. Among them, 51 strains of Gram-negative bacteria accounted for 60.71%, 30 strains of Gram-positive bacteria accounted for 35.71% and 3 fungal strains accounted for 3.58%, with statistical difference (P<0.05). The majority of Gram-negative bacteria were Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and the majority of Gram-positive bacteria were Staphylococcus epidermidis and Staphylococcus aureus. The resistance of Pseudomonas aeruginosa to ampicillin, cefazolin and ceftriaxone was high; that of Escherichia coli to ampicillin, cefazolin, ceftriaxone and aztreonam was high; that of Klebsiella pneumoniae to ampicillin, ceftriaxone and amikacin was high. Staphylococcus epidermidis was highly resistant to cefazolin, penicillin G and clindamycin, while Staphylococcus aureus was highly resistant to ciprofloxacin, penicillin G and clindamycin. Conclusion: Gram-negative bacteria were the main pathogens of nosocomial infection in patients with VVLE, and Gram-negative bacteria and Gram-positive bacteria were highly resistant to ampicillin, cefazolin, ceftriaxone, aztreonam, clindamycin, penicillin G and other antibiotics. The clinical treatment should be based on the results of drug sensitivity test.