Accommodating a patient's treatment preference has been reported to promote greater responsiveness and better clinical outcomes. The effect of administration route preference (ARP) on the individual analgesic response has not been extensively examined to date. This study aimed to investigate whether ARP-matched treatment, i.e., individualized intramuscular (IM) or oral (PO) analgesic administration according to patient choice, would increase the analgesic effect.In this prospective randomized study, we collected 38 patients with acute low back pain (aLBP) presenting at the emergency room of the Galilee Medical Center (Naharia, Israel) and asked them to report their ARP for analgesics. Regardless of their reported preference, they received either PO or IM diclofenac according to the treating physician's preference. Pain intensity was self-reported using the numeric pain score (NPS) before and during the first hour after drug administration.Both groups receiving PO or IM administration reported similar initial pain on admission, (NPS 8.63 ± 1.5 and 8.74 ± 1.6, respectively) and the same magnitude of pain reduction. However, patients who received the drug in their desired route (oral or injection) had a significantly greater reduction in pain levels (4.05 ± 2.8) as compared with patients who received the undesired route (2.08 ± 1.8), p < 0.05.These findings support the hypothesis that individualized ARP-matched treatment in aLBP improves therapeutic outcomes, although further studies with larger cohorts are needed.