IMPORTANCE: There is increasing interest in expanding use of minimally invasive pancreaticoduodenectomy (MIPD). This procedure is complex, with data suggesting a significant association between hospital volume and outcomes. OBJECTIVE: To determine whether there is an MIPD hospital volume threshold for which patient outcomes could be optimized. DESIGN, SETTING, AND PARTICIPANTS: Adult patients undergoing MIPD were identified from the Healthcare Cost and Utilization Project National Inpatient Sample from 2000 to 2012. Multivariable models with restricted cubic splines were used to identify a hospital volume threshold by plotting annual hospital volume against the adjusted odds of postoperative complications. The current analysis was conducted on August 16, 2016. MAIN OUTCOMES AND MEASURES: Incidence of any complication. RESULTS: Of the 865 patients who underwent MIPD, 474 (55%) were male and the median patient age was 67 years (interquartile range, 59-74 years). Among the patients, 747 (86%) had cancer and 91 (11%) had benign conditions/pancreatitis. Overall, 410 patients (47%) had postoperative complications and 31 (4%) died in-hospital. After adjustment for demographic and clinical characteristics, increasing hospital volume was associated with reduced complications (overall association P < .001); the likelihood of experiencing a complication declined as hospital volume increased up to 22 cases per year (95% CI, 21-23). Median hospital volume was 6 cases per year (range, 1-60). Most patients (n = 717; 83%) underwent the procedure at low-volume (≤22 cases per year) hospitals. After adjustment for patient mix, undergoing MIPD at low- vs high-volume hospitals was significantly associated with increased odds for postoperative complications (odds ratio, 1.74; 95% CI, 1.03-2.94; P = .04). CONCLUSIONS AND RELEVANCE: Hospital volume is significantly associated with improved outcomes from MIPD, with a threshold of 22 cases per year. Most patients undergo MIPD at low-volume hospitals. Protocols outlining minimum procedural volume thresholds should be considered to facilitate safer dissemination of MIPD.