IntroductionUp to 25% of colorectal cancer patients present with synchronous liver metastases that can be treated with two operations or a single ‘simultaneous’ operation. Morbidity and mortality appear similar between approaches, however changes in health-related quality-of-life following simultaneous resection are not well reported.MethodsA prospective, feasibility trial for simultaneous resection of synchronous colorectal liver metastases was conducted. Patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 and LMC21 at baseline (preoperatively), and 4 and 12 weeks postoperatively. Week 4 and 12 scores were compared with baseline using t-tests. Minimally important clinical differences were considered as a 10-point difference from baseline.ResultsC30 and QLQ-LMC21 were completed at baseline, 4 weeks, and 12 weeks by 39 (95%), 35 (85%) and 34 (83%) patients, and 39 (95%), 33 (80%) and 33 (80%) patients, respectively; 79% and 75% had at least one MICD according to QLQ-C30 at 4 and 12 weeks. At 4 weeks, physical functioning (mean difference (MD) − 11.9%, p = 0.002), role functioning (MD − 23.6, p = 0.007), and pain (MD + 19.7, p = 0.017) had significant worsening from baseline. At 12 weeks postoperatively, role functioning (MD − 19.7, p = 0.011) and fatigue (MD + 14.3, p = 0.03) were the only domains that remained significantly worse. By 12 weeks, pain and physical functioning had returned to baseline. There were no major demographic differences among those with and without an MICD at 12 weeks.ConclusionsSimultaneous resection of colorectal liver metastases led to clinically significant worsening fatigue and role functioning that persisted at 12 weeks post-surgery.