Purpose: To examine the cost-effectiveness of strategies for management of primary asymptomatic hyperparathyroidism (1) surgical strategies (2) medical follow-up vs. surgery for implementing European guidelines. Methods: A Markov model was used in a cohort of 55-year-old women (base-case) to estimate life-time costs and effectiveness of bilateral neck exploration (BNE), unilateral neck exploration (UNE), videoassisted parathyroidectomy (VAP), and life-long medical follow-up shifting for either BNE or UNE in case of disease progression. Data on localization tests, efficacy of the surgical procedures examined, adverse events were drawn from a systematic review of the literature (1970 – 2004). Quality of life adjustments were obtained from a convenience sample in the general population. Directs costs were estimated from the health care system perspective and discounted (base-case: 3%). Outcomes were expressed as qualited-ajusted life years (QALYs) and costs (Euros 2002). Each parameter was varied in sensitivity analyses. Results: For the base-case, (1) VAP strategy (VAPS) was the most effective, BNE strategy (BNES) was the least costly. UNE strategy (UNES) had an incremental cost-effectiveness ratio of € 2,688 vs. BNES and VAPS of € 17,250 per QALY vs. UNES. (2) Surgical management was more effective than medical follow-up with acceptable incremental cost-effectiveness ratios. VAPS became less effective than UNES over 71. Differences between UNES and VAPS were sensitive to small variations in efficacy and complication rates, QOL weights, and procedural costs. Medical follow-up strategies became the most effective if QOL weight for this condition was higher than 0.99. Conclusions: Cost-effectiveness analyses may be useful to guidelines developers faced with uncertainty. Sensitivity analyses allow them to identify the parameters that would be key in influencing the outcomes. Outcomes of surgical approaches for asymptomatic hyperparathyroidism had never been evaluated all together in randomized clinical trials. Moreover, only three studies explored the efficacy of medical follow-up compared to surgery. Furthermore, cost and quality of life had never been included according to the methodological standards in these comparisons. Our results suggest that, in an European context, surgery is more effective than medical follow-up at a reasonable cost and should be preferred except in patients without reduction in QOL for medical follow-up. Minimally invasive surgery is cost-effective compared to the traditional surgical approach. These results has been used to develop guidelines.