Objectives: Effective pain control after cardiac surgery may facilitate recovery. This study aimed to assess the use and association of ultrasoundguided single-injection chest wall blocks with liposomal bupivacaine on postoperative pain scores and short-term opioid requirements after cardiothoracic surgery at a single institution. Design: Retrospective cohort study. Setting: Midwestern academic hospital. Participants: Adult patients who underwent cardiothoracic surgery between July 1, 2020, and June 30, 2022. Interventions: Ultrasound-guided single-injection chest wall block with liposomal bupivacaine. Measurements and Main Results: Of the 1,038 patients included in this study, 301 (29%) received a perioperative nerve block for postoperative sternotomy pain, and 737 (71%) did not. Most of the single-shot blocks were bilateral parasternal intercostal plane blocks (n = 294 [98%]) performed after induction and before surgical incision (n = 280 [93%]). After adjusting for age, gender, American Society of Anesthesiologists status, select comorbidities, and surgical procedure type, mean postoperative pain scores were not significantly different between groups in the immediate postoperative period at all time points assessed (12 f 2 hours, 24 f 4 hours, 48 f 8 hours, and 72 f 12 hours). Similarly, there was no difference in mean opioid requirements (milligram morphine equivalents) at 72 hours between groups (68.6 [95% confidence interval, 56.383.4] vs 62.9 [95% confidence interval, 52.8-74.9], p = 0.195). Conclusions: In this retrospective study, the implementation of single-shot chest wall nerve blocks with liposomal bupivacaine was not associated with decreased postoperative pain scores or opioid consumption at 72 hours in select cardiac surgical patients at one institution. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.