Total pancreatectomy (TP) is rarely performed due to concerns for endocrine and exocrine insufficiency and decreased quality of life (QoL). Renewed interest is seen in recent years, but large cohort studies remain scarce. This study was designed to evaluate endocrine and exocrine insufficiency after TP and its impact on QoL.Adult patients (age ≥ 18 years) who underwent TP between 2008 and 2017 at Karolinska University Hospital with at least 6 months follow-up were included. Endocrine and exocrine insufficiency and QoL were assessed using validated questionnaires (EORTC QLQ-C30, QLQ-PAN26, PAID20, and DTSQs). Both pre- and postoperative questionnaires were available in a subgroup.Of 145 TP, 60 patients were eligible of whom 53 (88.3%) with a median of 21 months (interquartile range [IQR] 13-54) follow-up were included. Symptomatic hypoglycemia occurred in 90.6% (48/53) of patients, and 25% (12/48) experienced ≥ 1 episodes of loss of consciousness. The PAID20 revealed emotional burnout in seven patients (13.2%), whereas a high satisfaction score of diabetes treatment (median 28, IQR 24-32) was measured according to the DTSQs. Overall, 27 patients (50.9%) reported to have steatorrhea during a median of 2 days (IQR 0-4) in the past week. Overall QoL was reduced compared with a general population (66.7% vs. 76.4%; Δ9.7%) but did not differ with preoperative outcomes (n = 39, 66.7%; IQR 41.7-83.3 vs. 66.7%, IQR 50.0-83.3; P = 0.553) according to the EORTC QLQ-C30.Although the impact of endocrine and exocrine insufficiency on QoL after TP seems acceptable, the management of both insufficiencies should be further improved.