OBJECTIVE To determine the safety and efficacy of poly-N-isopropylacrylamide, a thermoresponsive adhesive, for sutureless sclerotomy closure in rabbits. METHODS Eight rabbits were randomized into three groups: short-term acute, mid-term chronic, and long-term chronic studies. A corresponding control group in which the scleral wounds were sutured by 6-0 vicryl sutures was assigned for each study group. A 20-gauge sclerotomy was performed following a core vitrectomy and 0.1 mL of 50 % liquid poly-N-isopropylacrylamide was applied to the scleral wounds. Before the polymer application, the scleral surface was raised above 32 °C using a halogen bulb lamp. Follow-up exams included color external and fundus photography, fundus fluorescein angiography, optical coherence tomography, and electroretinography. After the last follow-up assessment, the rabbits were sacrificed and histopathological studies on the scleral incision sites were performed. RESULTS Scleral wound healing was observed in the long-term chronic study rabbits. Histological studies were able to identify poly-N-isopropylacrylamide polymer at the sclerotomy site in the mid-term chronic study rabbits. Besides iatrogenic cataracts due to mechanical instrument touch in 2 rabbits, no other ocular abnormalities were identified in any of the eyes in the perioperative setting or during the follow-up period. Cornea, retina, and vitreous remained unaffected, and no abnormal inflammatory reaction or endophthalmitis was noticed in the 3 study groups. Filtering blebs indicative of leakage through the sclerotomies were not observed during the follow-up period. CONCLUSIONS Poly-N-isopropylacrylamide may provide effective in vitro scleral adhesion above 32 °C. Clinical studies are required to evaluate its utility in patients undergoing pars plana vitrectomy.