OBJECTIVES:A trial-based comparison of the use of resources, costs and health utility outcomes of fine-needle aspiration cytology (FNAC), and watchful observation for incidental small (< 2 cm) thyroid nodules was performed using data from the randomized controlled trial (RCT). METHODS:Using data from 314 patients, healthcare-related use of resources, costs, health utility, and quality-adjusted life years (QALYs) were estimated at 12 months after first presentation of incidental thyroid nodule(s) on an intention-to-treat basis with adjustment for covariates. Uncertainty about the incremental cost-effectiveness ratio for FNAC versus watchful management at 12 months of follow-up was incorporated using bootstrapping. Multiple imputation methods were used to deal with missing data. RESULTS:FNAC management was associated with greater use of healthcare resources and mean direct healthcare costs per patient (US$542.47 vs US$411.55). Lower mean 12-month QALYs per patient in FNAC was observed in comparison to watchful observation (0.752 versus 0.758). The probability that FNAC management was cost-effective compared with watchful management at a willingness-to-pay threshold of US50,000 per QALY gained was 26.5%. CONCLUSION:Based on 12-month data from RCT, watchful observation appeared cost-saving compared to FNAC in patients with incidental thyroid nodules that have a low-suspicion sonographic pattern and measure between 1.0 and 2.0 cm from healthcare provider perspective. CLINICALTRIALS. GOV IDENTIFIER:NCT02398721.