Background and aims: The study compared the effect of bilateral ultrasound-guided erector spinae plane block (ESPB) with varying bupivacaine concentrations on postoperative pain, shoulder tip pain, surgical stress response, dermatomal spread, and patient satisfaction in patients undergoing laparoscopic cholecystectomy (LC). Materials and methods: Patients were randomly assigned in three groups—group C (no block), group E2 [bilateral ultrasound-guided (USG) ESPB with 0.25% bupivacaine], and group E3 (bilateral USG ESPB with 0.375% bupivacaine). Results: Patients receiving ESPB had significantly lower numerical rating scale (NRS) scores at rest, during deep breathing, and on movement compared to the control. The E3 group had a reduced need for postoperative analgesics in a larger number of patients and also resulted in lower diclofenac consumption on the first postoperative day compared to the E2 group. A significant reduction in shoulder pain (SP) was seen in the E3 group compared to patients who did not receive any block. More than half of the patients in the E3 group did not require any analgesic in the 24 hours postoperative. A reduction in surgical stress with E3 was also indicated, and patients were more satisfied with their pain relief in ESPB groups compared to the control. In a first, dermatomal spread of ESPB in LC patients was studied and found to spread up to 8 and 10 dermatomes in the E2 and E3 groups, respectively. Conclusion: ESPB with 0.375% bupivacaine provides us with a much-desired alternative in LC patients in whom both opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) should be used cautiously, such as obese patients with reactive airway disease or renal dysfunction. The dose of bupivacaine should be calculated cautiously.