Objective: To study the effect of seamless nursing on stress level and complications in patients undergoing painless gastroscopy for the first time. Methods: A total of 106 inpatients receiving painless gastroscopy in Second Affiliated Hospital of Hainan Medical University from April 2020 to March 2021 were randomly divided into a control group (53 cases) and a study group (53 cases) by random number table method. Routine nursing was used in the control group and seamless nursing was used in the study group. The levels of physiological stress indexes[pulse (P), heart rate (HR), systolic blood pressure (SBP)] and complications were recorded and compared between the two groups at admission and 24 hours after nursing intervention. Results: Compared with SBP, HR and P of all patients before nursing, there was no significant difference (P>0.05); after nursing, SBP, HR and P water decreased significantly, and the study group was lower than the control group, the difference was statistically significant (P<0.05); the incidence of complications in the study group was significantly lower than that in the control group, the difference was statistically significant (P<0.05). Conclusion: Seamless nursing for patients undergoing painless gastroscopy for the first time can effectively improve the stress level of patients and reduce the incidence of complications, which has clinical application value and is worthy of popularization.