Abstract Aim The study aims to develop a protocol for the combined use of swaddling, facilitated tucking, expressed breast milk and sucrose administration methods in the orogastric tube (OGT) insertion procedure and evaluate its effectiveness. Methods The randomized controlled trial was conducted in the Neonatal Intensive Care Unit between 15 February 2022 and 15 September 2022, with 175 preterms. Preterms at 32–34 gestational weeks were randomly allocated to five groups: routine care, swaddling + expressed breast milk, swaddling + sucrose, facilitated tucking + expressed breast milk and facilitated tucking + sucrose groups. The data were collected using the Preterm Descriptive Information Form, the Physiological Measurement Form, the COMFORTneo scale and the Premature Infant Pain Profile (PIPP). Results The facilitated tucking + expressed breast milk method was found to be more effective than the routine care ( p distress < 0.001; p pain = 0.031) and swaddling + expressed breast milk ( p distress = 0.004; p pain = 0.015) methods in reducing the estimated distress and PIPP pain level of preterms during the procedure. Two minutes after the procedure, the facilitated tucking + expressed breast milk method was more effective than the routine care ( p < 0.001), swaddling + expressed breast milk ( p = 0.011) and swaddling + sucrose ( p = 0.002) methods in reducing the comfort level score. Conclusions The facilitated tucking + expressed breast milk method is effective in reducing pain and distress and providing comfort during the OGT procedure. Clinical Trials ID: NCT05180058.