Objective: To compare the effects of three types of ultrasound-guided nerve blocks on post-operative recovery quality in patients undergoing modified radical mastectomy for unilateral breast cancer. Methods: In this randomized double-blinded trial (chictr.org.cn, ChiCTR2200059428), 150 female patients were equally assigned to S group (serratus anterior plane block, SAPB) group, P group (paravertebral block, PVB) or ST group (serratus anterior combined with transverse thoracic muscle plane blocks, SA-TTMPB). The primary outcome was QoR-15 at five time points after surgery. Secondary outcomes were pain scores, time of first rescue analgesic and chronic pain incidence at 3 months. Results: The QoR-15 total score of S group at 24 h, 48 h, 72 h and 7 days post-surgery was significantly lower in groups P and ST, while there was no significant difference between groups P and ST (S vs. P vs. ST, 100.29 +/- 6.20 vs. 108.51 +/- 7.46 vs. 106.46 +/- 6.95; 105.59 +/- 6.18 vs. 113.06 +/- 7.44 vs. 111.22 +/- 6.56; 112.51 +/- 6.32 vs. 119.88 +/- 6.44 vs. 117.62 +/- 6.09; 123.00 +/- 5.78 vs. 128.86 +/- 5.96 vs. 126.92 +/- 5.72, p < 0.05). The dynamic and rest NRS scores at 6 and 12 h post-surgery were significantly higher in group S than in groups P and ST. Conclusion: Serratus anterior plane block combined with transverse thoracic muscle plane block and paravertebral block both have better effects than serratus anterior plane block alone in improving patients' early post-operative recovery quality, and also have an advantage in improving early post-operative pain. Clinical Trial Registration: chictr.org.cn (ChiCTR2200059428). Date of Registration: 29 April 2022. Significance: Serratus anterior combined with transverse thoracic muscle plane block may be a safer, easier, and equally effective nerve block strategy than paravertebral block in patients undergoing modified radical mastectomy for unilateral breast cancer.