Objectives: We aimed to compare the intraoperative and post-operative analgesic activities of the preventive applied serratus anterior plane (SAP) block and infiltration block in patients undergoing video-assisted thoracoscopic surgery (VATS). Methods: The study was carried out in 60 patients aged between 18 and 80 who were eligible for elective VATS, with the American Society of Anesthesiologists classification I-II, following ethical committee approval and written informed consent form. Patients were divided into two groups as SAP (group serratus anterior plane block [SAPB]) and group infiltration block after routine monitoring and general anesthesia induction by recording demographic data after randomization. Hemodynamic data of all patients were recorded before, after induction and within intraoperative 30 min period. Patient controlled analgesia (PCA) prepared with morphine was applied to all patients postoperatively. Intraoperative hemodynamic data and opioid consumption of patients, resting time, and coughing visual analog scale, time to first PCA dose, post-operative opioid consumption, rescue analgesic requirement, mobilization times, opioid side effects, and patient and surgical team’s satisfaction were evaluated. Results: Intraoperative hemodynamic data and opioid consumption were similar between the two groups. Post-operative pain scores (0 and 30 min, 1, 2, 4, 8, and 12 h) were lower in the SAPB group (p<0.005) and time to use the first PCA (p=0.002) was longer in the SAPB group. Post-operative PCA and rescue analgesic requirement were lower in the SAPB group (p=0.002, p=0.00). It was found that the first mobilization time was shorter in the SAPB group (p=0.003), and opioid-related side effects were similar in both groups (p=0.067). Patient and surgical team satisfaction was high in the SAPB group (p=0.004, p=0.000). Conclusion: As a result, more effective post-operative analgesia was provided with preventively SAPB, compared to infiltration block in patients undergoing VATS.