Background <p>Many patients have mixed feelings about end-of-life care, even when facing life-limiting conditions. Motivational interviewing might be useful for supporting patients in evoking reasons for advance care planning. This study aimed to examine the effects of an advance care planning program adopting motivational interviewing among palliative care patients.</p> Methods <p>A two-arm parallel randomized controlled trial was conducted between January 2018 and December 2019 in the palliative care clinics of two hospitals. Adult patients who were newly referred to palliative care services, with a score of 60 or higher in the Palliative Performance Scale and mentally competent, were eligible for the study. While all participants received palliative care as usual care, those in the intervention group also received the advance care planning program through three home visits. The primary outcome was the readiness to discuss and document end-of-life care decisions, and the secondary outcomes included decisional conflict, perceived stress, and quality of life.</p> Results <p>A total of 204 participants (mean [SD] age, 74.9 [10.8]; 64.7% male; 80.4% cancer) were recruited. Generalized estimating equation analyses showed a significant improvement in readiness for advance care planning behaviors in the intervention group compared with the control group at 3 months post-allocation (group-by-time interaction, appointing proxy: <i>β</i> = 0.80; 95% CI, 0.25–1.35; <i>p</i> = .005; discussing with family: <i>β</i> = 0.76; 95% CI, 0.22–1.31; <i>p</i> = .006; discussing with medical doctors: <i>β</i> = 0.86; 95% CI, 0.30–1.42; <i>p</i> = .003; documenting: <i>β</i> = 0.89; 95% CI, 0.36–1.41; <i>p</i> &lt; .001). The proportions of signing advance directives and placing a do-not-attempt cardiopulmonary resuscitation order were significantly higher in the intervention group, with a relative risk of 3.43 (95% CI, 1.55–7.60) and 1.16 (95% CI, 1.04–1.28), respectively. The intervention group reported greater improvements in social support and value of life than the control group immediately after the intervention. Significant improvements in decisional conflicts and perceived stress were noted in both groups.</p> Conclusions <p>Motivational interviewing was effective in supporting patients to resolve ambivalence regarding end-of-life care, thereby increasing their readiness for discussing and documenting their care choices.</p> Trial registration <p>ClinicalTrials.gov Identifier: NCT04162912 (Registered on 14/11//2019).</p>