Objectives: To compare the reliability of two different labial salivary gland biopsy (LSGB) incision techniques (vertical versus horizontal incision techniques) and to report the related complications and discomfort. Study Design: 163 patients who underwent LSGB were included in this study. Patients were randomly divided as vertical incision group (n=81) and horizontal incision group (n=82). Demographic and clinical information of each patient were recorded. A questionnaire was prepared and applied together with Visual Analog Scale (VAS) on the subjects verbally at the 7th day, postoperatively. Intraoperative, short- term and delayed complications were evaluated. Results: The mean age of patients (117 female, 46 male) was 47.3 years (range 19-79 years). Vertical incision technique was associated with less pain (p<0.001), less swelling (p<0.05), less scar formation (p<0.05) and less difficulty in eating (p<0.05) when compared with horizontal incision technique. No statistically significant differences were observed between the 2 groups in terms of hematoma, parasthesia and speech difficulty (p>0.05). Additionally, two subjects in the horizontal incision group revealed permanent paresthesia during the follow-up period of two years. Conclusions: This prospective study demonstrated that the subjects in the vertical incision group had less complication rates and discomfort after labial salivary gland procedure than those in the horizontal incision group.