Introduction Ultrasound and Tc99mMIBI scans are used to localise parathyroid tumours in sporadic primary hyperparathyroidism (pHPT). Intra-operative PTH (ioPTH) assay facilitates unilateral neck exploration (UNE). When both ultrasound and MIBI are negative, it is our policy to explore the left side of the neck and only proceed to bilateral neck exploration (BNE) when either a tumour is not found or when ioPTH does not fall to >50% of the highest pre-excision value. The aim of this study was to investigate the outcome of our approach to ‘double negative’ patients. Methods A retrospective analysis of patients undergoing primary parathyroidectomy for pHPT. Data were obtained from a prospective surgical database and the hospital electronic patient record. Results Between January 2004 and November 2014, 746 patients underwent a parathyroidectomy for pHPT. Those who did not have both pre-operative scans, ioPTH or a minimum of 6-month follow-up were excluded. Of 552 patients, 111 (20%) had double negative scans (group A), and in 441, either one or both scans were positive (group B). Median age was 61.5 years (range 10–88). Pre-operative PTH level was significantly lower in group A: 11.8 pmol/l (range 3.1–38.8) versus 14.9 pmol/l (range 2.8–101.6; P  < 0.01). Median tumour weight was significantly lower in group A: 280 mg (range 50–3710) versus 573 mg (range 10–12,000; P  < 0.01). Overall rate of multiple gland disease (MGD) was 11%; 24% in group A and 7% in group B ( P  < 0.01). Overall rate of UNE in Group A was 28% and converse to the rate in Group B (76%; P  < 0.01). Sensitivity and specificity of ioPTH to detect MGD were 98 and 98% in Group A versus 98 and 100% in Group B. First-time cure rate was 92.7% in group A and 96.8% in group B ( P  < 0.05). Conclusion A double negative scan is associated with small tumours and higher rates of MGD. Despite these challenges, surgery is successful in this group of patients reinforcing the message that negative localisation is not a contraindication for parathyroidectomy. We demonstrated that it is feasible to offer unilateral neck surgery to 28% of patients with double negative scans. A randomised trial is needed to compare BNE with ioPTH/UNE in this select population.