The prevalence of primary hyperparathyroidism (PHPT) is increasing and the majority (over 85%) are now asymptomatic and remain untreated. In order to know whether or not they can be left safely without surgery, issues on disease progression need to be addressed. We aimed to update the natural history of PHPT, with a focus of serum calcium progression in mild untreated patients, selected from a large pre-defined cohort of PHPT in Tayside, Scotland. Possible predictors of progression and the cure rate and outcomes of parathyroidectomy (PTX) were also addressed, corresponding to the Proceedings of the Third International Workshop on asymptomatic PHPT (2008). Using complete medical data at individual level, we identified 904 mild untreated patients (baseline calcium; 2.62 mmol/l) and 200 surgically treated patients (2.80 mmol/l). Their biochemical indices were followed up until September 2009, giving a median follow-up time of 4.7 and 5.8 years respectively. In patients with untreated PHPT, there was a decreased trend in calcium but an increasing trend in PTH for up to 12 years. Serum creatinine, alkaline phosphatase and cholesterol fluctuated around the normal ranges with no apparent trend. Disease progression, defined as an increase in calcium concentration, was observed in 121 patients (13.4%). Baseline age and PTH concentration were the only significant risk factors for disease progression. In comparison, in the PTX group, serum calcium was normalised after surgery in 196 patients (98%). Hospital admissions for renal stones and renal failure were reduced after successful surgery (P<0.01 in both instances) but not on cardiovascular disease, osteoporotic fractures or cancer. This observational study provides long-term results of treated and untreated PHPT and suggests that ~15% patients with mild untreated PHPT showed evidence of progression. PTH concentration was an important predictor of calcium progression.