Background: This study aimed to measure the least initial and maintenance forces of syringe and needle combinations to provide a reference for local anesthetic injection. Methods: An experimental study was conducted in our Physics Laboratory during September 2015. A series of syringes sized 1 mL, 3 mL, 5 mL, 10 mL and 20 mL were paired with the original needles, 27G, 27G spinal and 30G. Each combination was tested three times using a compression testing Instron 5940 Series to measure initial and maintenance forces. Statistical analysis was performed using One-way ANOVA. Results: The lowest initial force was shown by the combination of 1 mL syringe and 27G spinal needle. However, the 1 mL syringe showed no significant difference across the needles [F(3, 8) = 3.545; P < 0.068]. The original and 27G needle showed mean difference 0.28 (95%CI: −0.19, 0.75; P = 0.420). The lowest maintenance force was measured in the combination of 1 mL syringe and its original 26G needle. On the contrary, both the highest initial and maintenance forces were shown by the combination of 10 mL syringe and 30G needle. Conclusion: The 1 mL syringe with original 26G needle shows the best combination.