Background: To report the incidence and risk factors of suction loss during small incision lenticule extraction (SMILE).Methods: This retrospective comparative case control study included 8487 eyes of 4261 patients. Patients underwent SMILE surgery between January 2014 and September 2019 were included. Videos of suction loss were reviewed, and the direct causes of suction loss were noted. An independent samples t-test was used for comparisons between the suction loss group and the control group. A binary logistic regression model was used to determine the possible significant risk factors that might increase the likelihood of suction loss during SMILE surgery.Results: Suction loss occurred in 31 (0.37%) eyes of 30 patients; 23 (74%) cases occurred in the right eye (the first operative eye) and 8 (26%) cases occurred in the left eye. Among the 30 patients, 23 (76.7%) were male and 7 (23.3%) were female. The incidence in the six consecutive years were 0%, 2.13%, 0.34%, 0.24%, 0.22%, and 0.23%. Head and eye movements during surgery caused suction loss in 15 (48.4%) and 16 (51.6%) eyes, respectively. Comparison between the suction loss group and the control group showed that the first operative eye and male gender are at a significantly high risk for suction loss (p < 0.05).Conclusions: Surgical experience may influence the incidence of suction loss during SMILE surgery. The two events that easily led to suction loss were head and eye movements. The risk factors were first operative eye and male gender.Trial registration: Retrospectively registered. ChiCTR-ORC-17011040. Registered 1 April 2017. Name of registry: The observation of clinical results after corneal refractive surgery. Data of enrolment of the first participant to the trial: 1 January 2014.