Background Controversies exist in the best surgical approach (open vs. laparoscopy) to large adrenal tumours without peri-operative evidence of primary carcinoma, mainly due to possible capsular disruption of an unsuspected malignancy. In addition, intra-operative blood loss, conversion rate, operative time, and hospital stay may be increased with laparoscopy. The aims of our study were: (1) to compare clinical outcomes of laparoscopic adrenalectomy for large versus small adrenal tumours and (2) to identify risk factors associated with increased operative time and hospital stay in laparoscopic adrenalectomy. Methods This is a multicentre retrospective cohort study in a large patient population (N = 200) who underwent laparoscopic adrenalectomy in 2004–2014 at three Italian academic hospitals. Patients were divided into two cohorts according to tumour size: ‘‘large’’ tumours were defined as C5 cm (N = 50) and ‘‘small’’ tumours as \5 cm (N = 150). Further analysis adopting a C8 cm (N = 15) cut-off size was performed. Results The study groups were comparable in age and gender distribution as well as their tumour characteristics. The operative time (p = 0.671), conversion rate (p = 0.488), intra- (p = 0.876) and post-operative (p = 0.639) complications, and hospital stay (p = 0.229) were similar between groups. With a cut-off size C5 cm, the early study period (2004–2009), which included operators’ learning curve, was associated with increased risk of longer operative time (HR 0.57; 95 % CI 0.40–0.82), while American Society of Anaesthesiology score C3 was associated with prolonged hospital stay (HR 0.67; 95 % CI 0.47–0.97). Tumour size C8 cm was associated with prolonged operative time (HR 0.47; 95 % CI 0.24–0.94). Conclusions Surgeons skilled in advanced laparoscopy and adrenal surgery can perform laparoscopic adrenalectomy safely in patients with C5-cm tumours with no increase in hospital stay, or conversion rate, although operative time may be increased for C8-cm tumours. Surgeon’ experience, size C8 cm, and patient comorbidities have the largest impact on operative time and length of hospital stay in laparoscopic large adrenal tumour resection.