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Needle-free anesthetic delivery is a promising alternative to traditional anesthetic routes of administration. The purpose of this study was to determine the patient preference for and pulpal anesthetic efficacy of a 3% tetracaine plus 0.05% oxymetazoline (Kovanaze) nasal spray in maxillary lateral incisors and first premolars.Fifty adult subjects randomly received a 3% tetracaine plus 0.05% oxymetazoline (Kovanaze) nasal spray and mock infiltration or a mock nasal spray and 2% lidocaine with 1:100,000 epinephrine infiltration at the maxillary lateral incisor or first premolar in 2 appointments spaced at least 1 week apart in a single-blind cross-over design. Pulpal anesthesia was evaluated with an electric pulp tester. Side effects and subject preferences were also recorded.Anesthetic success was significantly lower for the Kovanaze nasal spray and mock infiltration (22%–37%) than for the mock nasal spray and lidocaine infiltration (89%–91%). Subjects reported more unwanted effects (nasal drainage and congestion, burning, pressure, and sinus congestion) after the Kovanaze nasal spray and mock infiltration than the mock spray and maxillary infiltration. Before participating in the study, more subjects (56%) preferred the nasal spray route versus a standard infiltration (44%). After experiencing both routes of administration, 100% of subjects preferred the standard infiltration.The 3% tetracaine plus 0.05% oxymetazoline (Kovanaze) nasal spray provided significantly less successful pulpal anesthesia than the lidocaine infiltration, was less preferable, and caused more unwanted effects.