Primary hyperparathyroidism (pHPT) occurs in about 90% of patients with multiple endocrine neoplasia type 1 (MEN1). In contrast to sporadic pHPT, multiple gland disease is most common in MEN1. The appropriate surgical approach is still controversial. The aim of this study was to analyze the results of surgical therapy of pHPT in patients with genetically confirmed MEN1. In an observational study, preoperative data, operative procedures, long-term results, and a possible genotype-phenotype correlation were analyzed in patients with pHPT and genetically confirmed MEN1. According to our results, tPTX+T (total parathyroidectomy+thymectomy+autotransplantation) seems to be a more favorable surgical approach in patients with MEN1 pHPT than sDE (selective gland exstirpation) and stPTX (subtotal parathyroidectromy) without cervical thymectomy, because recurrences or persistence of the disease are rare. A prospective randomized trial is needed to compare stPTX including cervical thymectomy vs tPTX+T. A genotype-phenotype correlation could not be identified.