Endoscopic ultrasound (EUS) has become a cornerstone in the diagnostic work-up of pancreatobiliary and mediastinal diseases. EUS-guided fine needle aspiration (FNA) and fine needle biopsy (FNB) provide high diagnostic yield with a generally low risk profile. However, procedure-related complications still occur and may have multiple contributing factors, especially when EUS is performed together with ERCP. The present study aimed to evaluate the incidence, type, and clinical outcome of complications following EUS-guided tissue acquisition in a tertiary referral center over a seven-year period.

All EUS procedures performed between December 2018 and September 2025 were retrospectively reviewed. Demographic and procedural data were collected, including type of needle, number of passes, puncture route, and clinical course. Complications were classified according to their type, timing, and severity. Cases with combined EUS–ERCP were analyzed separately. Descriptive statistics were used to summarize the findings.

During the study period, 2,759 EUS procedures were performed, of which 1,237 involved tissue sampling (EUS-FNA or EUS-FNB). Complications occurred in 89 patients (7.2%). The mean age of affected patients was 66.6 years (median 68, IQR 57–75), and 49% were male and 45 (50.6%) were female. Most procedures were performed with FNB (91%) using a 22G needle (92%), with a median of three needle passes. The median hospital stay was five days (IQR 4–6).

Of all complications, 47.2% occurred after combined EUS–ERCP and 52.8% after EUS alone. The most frequent event was pancreatitis (n=65; 73%), including five severe cases (5.6%) and two deaths. Other complications included cholecystitis (n=6), bleeding-related events (n=6), sepsis (n=3), peritonitis (n=2), intracystic hemorrhage (n=3; one fatal), and several isolated events such as retroperitoneal hematoma and hemoperitoneum (two fatal). Overall, four patients (4.5%) died due to procedure-related complications. Conservative management was effective in 95.5% of cases, while two patients required interventional and two-surgical treatment. The procedure-related mortality rate was 0.32% among EUS-FNA/FNB cases and 0.15% of all EUS procedures.

EUS-guided tissue acquisition remains a safe diagnostic procedure with a low complication rate and very low mortality. Nearly half of all complications were observed in combined EUS–ERCP sessions, highlighting the complex interplay of risk factors in such cases. Most complications were mild pancreatitis managed conservatively, while bleeding and infectious events were rare and effectively treated. These real-world data confirm that EUS-FNA and EUS-FNB are safe and reliable when performed in experienced hands within a high-volume center.