Purpose: The study investigated the rate of complications associated with sonographically guided lymph node biopsies and assessed potential risk factors. Methods: A total of 536 sonographically guided puncture procedures (283 males, 52.8%; 253 females, 47.2%; average age 57.0 ± 16.0 years; range 14 -87 years) were performed in 469 patients for the work-up of unclear lymphadenopathy. Events, complications and potential risk factors, were prospectively documented. Results: The 469 patients underwent a total of 536 puncture procedures (PP) including 663 punctures and 1485 passes. Lymph node localizations were intraabdominal (55.2%, n = 296), cervical (22.4%, n = 120), inguinal (12.9%, n = 69), axillary (7.8%, n = 42) and other (1.7%, n = 9). No complications were documented during the entire study period. There was no increased risk of complications documented for the potential risk factors number of punctures, the number of passes, the localization, diameter of the lymph node (s), puncture technique, needle gauge, as well as patients' sex, age and coagulation parameters, and the experience of the examiner. Conclusions: Our findings confirm the safety of percutaneous sonographically guided lymph node biopsies in different regions of the body in patients with adequate coagulation parameters undergoing pre-interventional color Doppler ultrasound examination.