The safety of a technique for ultrasound–guided biopsy of renal allografts was evaluated based on 348 consecutive procedures in cynomolgus monkeys. A spring-loaded biopsy device with an 18G tru-cut biopsy needle was used to biopsy renal allografts in 139 cynomolgus monkeys performed either on clinical indication (n = 95 animals) or as serial protocol biopsies (n = 44 animals) for a total of 348 biopsies. Monkeys having serial biopsies received between 3–9 biopsies per animal. All others received non-protocol biopsies that were performed on clinical indication, and the range was 1–15 biopsies per animal. No life-threatening complications or deaths occurred and there were no clinically detectable minor complications such as macrohematuria. Self–limiting complications such as small arteriovenous fistulas (n = 4, 3–5 mm large) were detected with Doppler ultrasound and resolved hemodynamically after 2–4 weeks. Three animals developed hematomas ranging 4 mm-2 cm in diameter and were no longer sonographically evident 2–4 weeks later. Ultrasound–guided biopsy of renal allografts can be performed with a high degree of safety in small (3–5 kg) laboratory animals such as the cynomolgus monkey and provides a valuable tool for renal transplantation research. Even when cores were taken at two week intervals no major complications occurred and only rarely were clinically irrelevant complications detected. Experience with diagnostic ultrasound, both gray scale and Doppler, is important for both safety and the recognition of complications that may arise.