ObjectivesThis study aimed to assess the effect of needle insertion angle on pain during labial infiltration anesthesia in the anterior maxillary region.Material and MethodsIn this parallel‐design randomized clinical trial, participants were randomly assigned to four groups for labial infiltration anesthesia of the anterior maxilla. Local anesthesia was performed with needle orientation parallel to the longitudinal axis of the tooth using a conventional syringe (Syringe‐0), needle at α angle with a conventional syringe (Syringe‐α), computer‐controlled local anesthetic delivery (CCLAD) device parallel to the longitudinal axis of the tooth (CCLAD‐0), and CCLAD at α angle (CCLAD‐α). The heart rate (HR), blood pressure (BP), and respiratory rate (RR) of participants were measured before needle insertion, immediately after needle insertion, and immediately after the injection by a vital signs monitor. The level of pain experienced by participants was quantified using a numerical rating scale (NRS). Data were analyzed by repeated‐measures ANOVA and regression models (α = 0.05).ResultsThirty‐six participants aged from 21 to 60 years, with a mean age of 35.36 years were recruited. The mean pain scores were 7.44, 4.67, 2.89, and 0.67 in groups Syringe‐0, Syringe‐α, CCLAD‐0, and CCLAD‐α, respectively (p < 0.001). Age and sex had no significant effect on pain scores (p = 0.914 and p = 0.702, respectively). The four groups had no significant difference in vital signs (p > 0.05).ConclusionsInjection at an α angle and the application of CCLAD can be used in clinical practice to decrease the pain experienced by participants during labial infiltration anesthesia of the anterior maxilla.Trial RegistrationIranian Registry of Clinical Trials: IRCT20230719058849N1.