Background: An interscalene brachial plexus block is a commonly conducted nerve block for anesthesia and analgesia in shoulder surgery. Due to its proximity to the targeted nerve, the phrenic nerve, which innervates the diaphragm, is typically inadvertently blocked by ventral spread of the local anesthetic. Although hemidiaphragmatic paresis is tolerable in healthy patients, it would be an irreversible risk to patients with compromised lung reserve. Objectives: To investigate the effect of interscalene brachial plexus block on hemidiaphragmatic paresis by comparing the conventional local anesthetic volume with a reduced experimental volume at a more specific position using an ultrasound-guided 2-point injection technique. Study Design: Prospective, randomized controlled study registered with the Clinical Trial Registry of Korea (https://cris.nih.go.kr/cris/index.jsp. KCT0005575. 04/11/2020). Setting: This study was conducted at a single hospital affiliated with an academic institution between April and December 2020. Methods: Patients undergoing brisement manipulation and arthroscopic shoulder surgery were randomized to the experimental (10 mL of ropivacaine 0.5%) and control groups (15 mL of ropivacaine 0.5%). Fifty-two patients who received an interscalene brachial plexus block for anesthesia and analgesia in the shoulder region. The interscalene block was performed using a 2-point injection and observing the spread pattern of the local anesthetic. The primary outcome was the incidence of hemidiaphragmatic paresis, estimated by the thickening fraction of the diaphragm. The secondary outcomes included oxygen saturation, presence of dyspnea, resting pain score, and handgrip strength score. Results: Thickening fraction was significantly decreased in the control group compared with the experimental group (median [interquartile range], 13.9 [10.0–18.5] versus 28.5 [14.5–38.8], P < 0.001). The incidence of hemidiaphragmatic paresis was significantly higher in the control group than in the experimental group (92.3% versus 53.8%, P = 0.004). Handgrip strength was significantly reduced in the control group compared with the experimental group (P = 0.029). Limitations: We did not perform a phrenic nerve conduction study, as it is rarely performed in routine clinical operations. We did not formally assess the distance and spatial relationship of the phrenic nerve to the targeted nerve. Outcome variables including pain assessment were limited to the immediate postoperative period. Conclusions: Reducing the local anesthetic volume by selective injection and observing the spread pattern resulted in a decreased incidence of hemidiaphragmatic paresis and preserved handgrip strength after interscalene block.