Objective: To investigate the 5-year effect of surgeon experience with laparoscopic Nissen fundoplication (LNF). In 2000, a randomized controlled trial (RCT) was prematurely terminated because LNF for gastroesophageal reflux disease was associated with a higher risk to develop dysphagia than conventional Nissen fundoplication (CNF). Criticism focused on alleged bias caused by the relative lack of experience with the laparoscopic approach of the participating surgeons. Design: Multicenter RCT and prospective cohort study. Setting: University medical centers and tertiary teaching hospitals. Patients: In the RCT, 74 patients underwent CNF and 93 patients underwent LNF (LNFI). The complete setup of the cohort study (LNFII) (n=121) mirrored the RCT, except that surgeon experience increased from more than 5 to more than 30 LNFs per surgeon. Interventions: Conventional Nissen fundoplication, LNFI, and LNFII. Main Outcome Measures: Intraoperative and in-hospital characteristics, objective reflux control, and clinical outcome. Results: In LNFII, operating time (110 vs 165 minutes; P<.001), dysphagia (2.5% vs 12.3%; P=.008), dilatations for dysphagia (0.8% vs 7.0%; P=.02), and conversions (3.5% vs 7.7%; P=.19) were reduced compared with LNFI. Moreover, in LNFII, hospitalization (4.2 vs 5.6 days; P=.07 and 4.2 vs 7.6 days; P<.001) and in-hospital complications (5.1% vs 13.5%; P=.046 and 5.1% vs 19.3%; P=.005) were reduced compared with LNFI and CNF, respectively. In LNFII, the 6-month reintervention rate was reduced compared with LNFI (0.8% vs 10.1%; P=.002). Esophagitis and esophageal acid exposure at 3 months and reflux symptoms, proton-pump inhibitor use, and quality of life at 5 years improved similarly. Conclusions: Operating time, complications, hospitalization, early dysphagia, dilatations for dysphagia, and reintervention rate after LNF improve significantly when surgeon experience increases from more than 5 to more than 30 LNFs. In contrast, short-term objective reflux control and 5-year clinical outcome do not improve with experience. In experienced hands, LNF reduces in-hospital complications and hospitalization compared with CNF, with similar 5-year effectiveness and reoperation rate.