Primary hyperparathyroidism in multiple endocrine neoplasia type I usually affects all parathyroid glands, making focused parathyroidectomy (FP) inappropriate. The risk of previously undiagnosed multiple endocrine neoplasia type I in a younger patient with primary hyperparathyroidism is higher than in an older patient. We hypothesized that FP may lead to a higher failure rate in younger versus older patients. A retrospective review was performed of a single-institution database of patients who underwent parathyroidectomy for primary hyperparathyroidism. Routine statistical analysis was performed, including Fisher's exact test. A total of 635 patients were included. Operative failure occurred in 7/55 (13%) younger patients and 21/580 (4%) older patients (P = 0.007). In conclusion, operative failure occurred in a statistically significantly higher percentage of younger versus older patients undergoing FP. This is partly explained by undiagnosed multiple endocrine neoplasia syndrome type I in the younger patient group. Endocrine surgeons must make every effort to preoperatively identify multiple endocrine neoplasia syndrome type I in the younger patient population.