Uniportal video-assisted thoracoscopic surgery (U-VATS) can achieve comparable traditional clinical outcomes as those of multiportal video-assisted thoracoscopic surgery (M-VATS). This study aimed to compare patient-reported outcomes between U-VATS and M-VATS for lung cancer lobectomy in the early postoperative period.This comparative analysis used data from a longitudinal prospective study (CN-PRO-Lung 1). Symptom severity, functional status, and quality of life were compared between groups using generalized estimation equation models. Symptom severity and functional status were reported as proportion of patients with clinically meaningful severe scores on 0-10-point scales assessed using the MD Anderson Symptom Inventory-Lung Cancer module.Of the 174 patients included, 102 (58.6%) underwent U-VATS lobectomy and 72 (41.4%) underwent M-VATS lobectomy. After adjusting for confounders, patients in the U-VATS group reported less severe pain (p = 0.02), fatigue (p = 0.001), constipation (p = 0.01), coughing (p = 0.003), shortness of breath (p < 0.001), and disturbed sleep (p = 0.007) during the 6-day postoperative hospitalization than those in the M-VATS group. Moreover, fewer patients reported severe impairment to walking (p = 0.033) or their capacity to enjoy life (p = 0.027) in the U-VATS group. Meanwhile, there were no significant between-group differences in the quality of life scores, operative time, chest tube duration, length of hospital stay, or early complication rate (≥ grade II) (all p ˃ 0.05).U-VATS might produce fewer severe symptoms and better functional status than M-VATS for lung cancer lobectomy in the early postoperative period.Copyright © 2021. Published by Elsevier Inc.