Background <p>Loss of appetite and weight loss are major concerns in patients with pancreatic cancer. The aim of this study was to evaluate the associations of corticosteroid therapy with weight change and appetite in the long term, in patients with advanced pancreatic cancer.</p> Methods <p>This was a post hoc analysis of the previously performed randomized, controlled MISTRAL trial in patients with advanced pancreatic cancer. Data on weight and appetite at baseline and after approximately 1, 2, 3 and 4&#xa0;months were used. The association between corticosteroid exposure and weight change was calculated using mixed linear regression, models adjusted for sex, age, randomization arm and performance status. Appetite was analyzed comparing those without and with corticosteroids during 3 days before appetite assessment.</p> Results <p>Two hundred forty-four patients (121 women) were included. Patients who received corticosteroid therapy at any time during the 4&#xa0;months had less appetite (<i>p</i> &lt; 0.001), lower performance status (<i>p</i> &lt; 0.001) and lower BMI (<i>p</i> &lt; 0.05) compared to those not receiving corticosteroids. Patients receiving corticosteroids had a larger weight loss of on average 1.48% during a month of follow-up compared to those not receiving corticosteroids (<i>β</i> − 1.48, 95% CI =  − 2.11 to − 0.84). Patients exposed to corticosteroids reported poorer appetite at every time point than those not exposed.</p> Conclusion <p>In long-term follow-up, corticosteroid treatment was associated with greater weight loss and poorer appetite among patients with advanced pancreatic cancer. These findings may partly be explained by a higher symptom burden among patients receiving corticosteroids. Future prospective trials are warranted to clarify the effect of long-term corticosteroid treatment on weight and appetite.</p>