Background: People with intellectual disabilities have a higher prevalence of certain chronic diseases and higher avoidable mortality. Some of these diseases or their exacerbation could be avoided through disease prevention and health promotion interventions, as people with intellectual disabilities have high rates of unhealthy eating habits, stress, lower levels of mobility and similar addictive behaviours to the general population. At the same time, they face significant barriers to accessing preventive healthcare interventions.Objective: To test the effectiveness of an advanced practice nurse-led case management and prevention intervention for people with intellectual disabilities on health status after 12 months.Design: Two-arm parallel randomised-controlled trial with waiting list.Setting(s): Community setting in an urban area of Hamburg, Germany.Participants: 214 adults with an ICD-10 diagnosis F70-79 and a care level below 4 according to German Social Code XI, who were not at the end-of-life.Methods: The intervention consisted of case management, social space analysis, prevention planning and counselling in four outreach home visits on the topics of addiction, mobility, nutrition and stress. The control group received usual care. Participants were allocated using permuted block randomisation. The primary outcome was health status (WHODAS, 0-100) at 12 months (t2). Secondary outcomes were health status at 6 months (t1), resilience (RS-11, 7-77) and health-related quality of life (EQ5D, 0-100) at t1 and t2. Lower scores indicate better health status and higher scores better resilience and quality of life. Raters and analysts were blinded. Analyses were performed with ANCOVAs and Bonferroni correction to α= 0.025 and 97.5% confidence intervals (CI).Results: We randomised 107 participants to each group. For the primary outcome health status at t2 (n=167), the mean difference (MD) was -4.38 (CI: -8.13 to -0.62, ή²= 0.041). For the secondary outcome of health status at t1, the MD was -1.06 (CI: -3.51 to 5.62, ή²= 0.002). For resilience, the MD was +0.51 (CI: -3.11 to 2.10, ή²= 0.001) at t1 and +2.70 (CI: -5.78 to 0.39 ή²=0.022) at t2. For health-related quality of life, a MD of +0.72 (CI: -5.88 to 7.32, ή²=0.000) at t1 and -1.19 (CI: -8.71 to 6.33 ή²= 0.001) at t2 were measured.Conclusions: Overall, a nurse-led intervention focusing on prevention and case management can lead to a statistically significant change in health after 12 months, but not for the secondary outcomes. The current literature on minimal clinically important differences indicates that the effect is also clinically important.