Purpose: Breast cancer surgery - with or without axillary lymph node dissection - often results in significant early postoperative morbidity due to pain. Pre-incisional thoracic paravertebral block (TPVB) provides postoperative analgesia for up to 48 hours. We prospectively studied the quality of postoperative analgesia and the subjective wellbeing in patients who underwent breast cancer surgery under combined general anesthesia and TPVB. Materials and Methods: After institutional review board approval, 206 patients undergoing primary breast cancer surgery or subsequent reconstructive breast surgery under general anesthesia and TPVB (single-injection of ropivacaine 0.5% 20 ml at the T3 level) were studied. The primary outcome variables were the pain scores at rest and with exercise, as determined by an 11-tier visual analog scale (0 = no pain, 10 = worst pain imaginable). Secondary variables included the frequency of supplemental intravenous analgesic medication, TPVB-related complications, and subjective satisfaction of the patients. Results: TPVB provided complete (VAS = 0) or effective analgesia (VAS = 4) in 88.4% of all patients during the entire observation period of 48 hours after surgery. Pain scores decreased significantly at 24 and 48 hours after surgery when compared to the first VAS value, which was determined on discharge from the post-anesthesia care unit (rest) or 6 hours after surgery (excercise), respectively (p < 0.001). Within the first 48 hours after surgery, 22% of the patients requested metamizole or acetaminophen, while another 11% required an additional opioid for pain relief. Patient satisfaction was high with the analgesic regimen, and was rated "excellent or good" by 181 (87.9%) patients, "fair" (n = 14; 6.8%) or "poor" (n = 11; 5.3%). Two pneumothoraces occurred in our patients, which were TPVB-related complications. Conclusion: Combined general anesthesia and pre-incisional, single-injection TPVB for breast cancer surgery is an effective and technically simple analgesic regimen that produces a high level of patient satisfaction and procedural safety.