Introduction: The intertransverse process block is increasingly used to ameliorate postoperative pain following a plethora of surgical procedures involving the thoracic wall. Nevertheless, the optimal approach and cutaneous extent of the sensory block are currently unknown. We aimed to further describe the intertransverse process block, single injection versus multiple injection, and we hypothesized that the single-injection intertransverse process block is a non-inferior technique. Methods: Twelve healthy male volunteers were cross-over randomized to receive either single-injection intertransverse process block with 21 mL ropivacaine 7.5 mg/mL, including two sham injections, at the thoracic level T4/T5 or multiple-injection intertransverse process block with three injections of 7 mL ropivacaine 7.5 mg/mL at the thoracic levels T2/T3, T4/T5 and T6/T7 at the first visit. At the second visit, the other technique was applied on the contralateral hemithorax. A non-inferiority margin of 1.5 anesthetized thoracic dermatomes was chosen. Results: The mean difference (95% CI) in the number of anesthetized thoracic dermatomes was 0.82 (-0.41 to 2.05) pnon-inf<0.01 indicating non-inferiority favoring the single-injection technique. Both techniques anesthetized the ipsilateral thoracic wall and demonstrated contralateral cutaneous involvement to a variable extent. The multiple-injection intertransverse process block anesthetized a significantly larger cutaneous area on the posterior hemithorax and decreased mean arterial pressure at 30 and 60 min postblock application. Thoracic thermography showed no intermodality temperature differences yet compared with baseline temperatures both techniques showed significant differences. Conclusions: Single-injection intertransverse process block is non-inferior to multiple injection in terms of anesthetized thoracic dermatomes. Both techniques generally anesthetize the hemithoracic wall to a variable extent. EU clinical trials register: 2022-501312-34-01.