Whipple's disease (WD) is a rare and potentially fatal infectious disease caused by Tropheryma whipplei. We aimed to identify the clinical and laboratory predictors of immune reconstitution inflammatory syndrome (IRIS), currently the most important complication of WD. At the time of diagnosis of WD, erythrocyte sedimentation rate and platelet count differed significantly between patients who subsequently developed IRIS and those who did not. Low ESR and PLT count at diagnosis help identify WD patients at high risk of developing IRIS.