Background: With increased early lung cancer screening, synchronous multiple pulmonary nodules are more frequently detected. However, due to the lack of standardized treatment strategies, their management remains contentious. This study utilizes patient-reported outcomes (PROs) to assess early postoperative symptoms and functionality, aiming to determine the optimal resection extent for unilateral multiple pulmonary nodules. Methods: In this longitudinal cohort study, 550 patients undergoing single-port video-assisted thoracoscopic surgery (VATS) for pulmonary nodules were categorized into two groups based on resection extent: single-lobe and multiple-lobe. The Perioperative Symptom Assessment for Patients Undergoing Lung Surgery (PSA-Lung) scale was used to measure symptom severity, functional status, and short-term outcomes preoperatively, daily from postoperative days 1-4, and weekly up to four weeks post-surgery. Mixed-effects models were used to compare the differences in PRO scores over time. Results: Among the participants, 416 had single-lobe and 134 had multiple-lobe surgeries. The multiple-lobe group reported significantly worse symptoms of pain (P=0.04), shortness of breath (P<0.001), disturbed sleep (P=0.007), and fatigue (P=0.01), along with greater functional impairments in walking (P=0.002) and daily activities (P=0.002). We then analyzed the distribution of postoperative moderate-severe symptoms and functional impairment in both groups. We found that the proportion of patients with moderate-to-severe shortness of breath (P<0.001), disturbed sleep (P<0.001), difficulty in walking (P=0.001), and difficulty in daily activities (P<0.001) was significantly higher in the multiple-lobe group than in the single-lobe group. Moreover, patients with multiple-lobe surgeries had a longer recovery time from pain (P=0.02) and drowsiness (P=0.005) than those with single lobe surgeries. As a matter of course, surgical times were significantly longer in the multiple-lobe group than in the single-lobe group. Conclusions: Multiple-lobe surgery patients faced more severe postoperative symptoms and functional impairments, with extended recovery times. These results advocate for a conservative surgical approach, favoring long-term monitoring over extensive resection for patients with unilateral multiple nodules without clear signs of malignancy or progression.