Introduction Levodopa‐carbidopa intestinal gel (LCIG) infusion has demonstrated to improve motor fluctuations. The aim of this study is to assess the long‐term safety and effectiveness of LCIG infusion in advanced Parkinson's disease (PD) patients with motor fluctuations and its effect in nonmotor symptoms. Methods Adverse events (AE) and their management, clinical motor, and nonmotor aspects were assessed up to 10 years. Thirty‐seven patients were treated with LGIC; in three subsets of patients, specific batteries of tests were used to assess cognitive and behavior assessment for 6 months, quality of sleep for 6 months, and quality of life and caregiver burden for 1 year. Results There was a high number of AE, but manageable, most of mild and moderate severity. All patients experienced significant improvement in motor fluctuations with a reduction in mean daily off time of 4.87 hr after 3 months (n = 37) to 6.25 hr after 9 years (n = 2). Diskynesias remained stables in 28 patients (75.7%) and improved in 5 patients (13.5%). There was no neuropsychological deterioration, but an improvement in attentional functions, voluntary motor control, and semantic fluency. Quality of sleep did not worsen, and there was an improvement in the subjective parameters, although overnight polysomnography did not change. There was a significant sustained improvement of 37% in PD‐Q39 after 3 months and to 1 year, and a significant reduction in caregiver burden of 10% after 3 months. Conclusion LCIG infusion is a safe and efficacious treatment for the control of motor fluctuations, and for improvement or nonworsening of nonmotor aspects, long‐term sustained, and feasible for use in routine care. This long‐term safety and effectiveness study of levodopa‐carbidopa intestinal gel (LCIG) infusion in advanced Parkinson's disease patients with motor fluctuations and its effect in nonmotor symptoms concludes that LCIG infusion is a safe and efficacious treatment for the control of motor fluctuations, and for improvement or nonworsening of cognition and behavior, quality of sleep and improvement of quality of life and caregiver burden, long‐term sustained, and feasible for use in routine care.