This prospective randomized controlled trial aimed to evaluate and compare patient response to a conventional syringe and a computer-controlled local anesthetic delivery system (CCLAD) both immediately and after reflection time, including the impact of anesthesia duration. Methods: Twenty adult patients (10 men and 10 women) with at least two tooth-neck defects each in different quadrants were treated with local buccal infiltration anesthesia. Using split-mouth design, one quadrant was anesthetized using a conventional syringe, the other with CCLAD. The time elapsed between time of injection and time of disappearance of numbness was recorded. Patients were asked to mark on a Visual Analog Scale their visual impression of the device regarding anxiety-inducement, their sensation of mucosal puncture, pain during administration, and pain perception during treatment for the two different methods as well as future preference immediately after treatment and after reflection time. Results: The level of anxiety-inducement and pain during administration were ranked three times higher with the conventional syringe (35.95%-11.85%, p < 0.001 and 21.3%-7.7%, p ¼ 0.005, respectively). There was no difference in mean sensation of mucosal puncture, nor a statistically significant correlation between duration of administration and time until disappearance of numbness. Once anesthesia was administered, no pain during treatment was detected using either method. Patients' preference of methods changed significantly with time in favor of CCLAD (p ¼ 0.01). Conclusions: The use of CCLAD increased patients' comfort visually and in terms of administration; patients' preference in favor of CCLAD increased with time. Clinical significance: Patients' preference of CCLAD over against the conventional syringe, even more so after reflection time, can imply the preference of CCLAD for clinicians, too, in order to enhance patients' and clinicians' comfort.