Harvesting of liver samples for toxicologic and other laboratory analyses is frequently undertaken in free-ranging fish to evaluate accumulations of various pollutants and chemicals. However, commonly used, lethal techniques for collecting liver tissues are unacceptable when dealing with protected species. We report the use of a nonlethal, single-entry, endoscopic technique using saline infusion to examine and collect large liver samples using optical biopsy forceps from 16 free-ranging sturgeon (Scaphirhynchus spp.) during 25 and 27 January 2010. Under tricaine methanesulfonate anesthesia and following the introduction of the optical biopsy forceps (with a 5-mm telescope) through a 1–2-cm ventral midline skin incision, liver examination and collection of biopsies averaging 0.9 g, ranging up to 1.4 g, and representing up to 12% of total liver tissue were successful. All fish made uneventful recoveries and necropsy examinations the following day failed to indicate any significant hemorrhage or iatrogenic trauma. We recommend the use of large optical biopsy forceps as a practical, nonlethal alternative for collection of large liver biopsies from sturgeon and other fish.