Background: An erector spinae plane block (ESPB) has gained popularity due to its effectiveness and simplicity for pain relief. However, it is uncertain whether an ESPB provides superior analgesia after a VATS or thoracotomy compared to other regional and systemic analgesic techniques. Methods: A retrospective cohort study was conducted from January to June 2023 comparing an ESPB with intravenous combination analgesia (IV–CA) in VATS patients and with thoracic epidural analgesia (TEA) in thoracotomy patients. The primary endpoint was the opioid demand during the first two hours in the post-anesthesia care unit (PACU). The secondary outcomes included the pain scores and adverse events. Results: A total of 61.2% of the 165 included VATS patients and 56.9% of the 72 thoracotomy patients were treated with an ESPB. Following a VATS, an ESPB decreased the median piritramide demand (7.5 [3.0 to 12.0] vs. 10.5 [6.5 to 15.5] mg, p < 0.01). However, after a thoracotomy, an ESPB increased the median piritramide demand (12.0 [6.0 to 15.0] vs. 3.0 [0.0 to 9.0] mg, p < 0.01). The pain scores and adverse events were similar between the groups. Conclusions: An ESPB reduces the piritramide demand in VATS patients compared with IV–CA, providing similar pain relief. However, in thoracotomy patients, an ESPB is associated with an increased piritramide demand compared to TEA. An ESPB is an attractive add-on to IV–CA after a VATS, while TEA remains the gold standard after a thoracotomy.