The relapse into undernutrition after nutritional recovery among those enrolled in a nutritional program is a common challenge of nutritional programs in HIV care settings, but there is little evidence on the determinants of the relapse. Nutritional programs in HIV care settings in many countries are not well designed to sustain the gains obtained from enrolment in a nutritional program. This study examined relapse into undernutrition and associated factors among people living with HIV in the Tigray region of Ethiopia. The study employed a mixed-methods approach, involving quantitative and qualitative studies. Among those who graduated from the nutritional program, 18% of adults and 7% of children relapsed into undernutrition. The mean time to relapse for adults was 68.5 months (95% CI, 67.0–69.9). Various sociodemographic, clinical, and nutritional characteristics were associated with a relapse into undernutrition. A considerable proportion of adults and children relapsed after nutritional recovery. Food insecurity and poor socioeconomic status were a common experience among those enrolled in the nutritional program. Hence, nutritional programs should design strategies to sustain the nutritional gains of those enrolled in the nutritional programs and address the food insecurity which was reported as one of the contributors to relapse into undernutrition among the program participants.