This study aimed to comparatively analyze the effect of the person-centered prescription (PCP) model on pharmacotherapeutic indicators and the costs of pharmacological treatment between a dementia-like trajectory and an end-stage organ failure trajectory, and two states of frailty (cut-off point 0.5). A randomized controlled trial was conducted with patients aged ≥65 years admitted to a subacute hospital and identified by the Necessity of Palliative Care test to require palliative care. Data were collected from February 2018 to February 2020. Variables assessed included sociodemographic, clinical, degree-of-frailty, and several pharmacotherapeutic indicators and the 28-day medication cost. Fifty-five patients with dementia-like trajectory and 26 with organ failure trajectory were recruited observing significant differences at hospital admission in the mean number of medications (7.6 vs. 9.7; p < 0.004), the proportion of people on more than 10 medications (20.0% vs. 53.8%; p < 0.002), the number of drug-drug interactions (2.7 vs. 5.1; p < 0.006), and the Medication Regimen Complexity Index (MRCI) (25.7 vs. 33.4; p < 0.006), respectively. Also, regarding dementia-like patients, after application of the PCP model, these patients improved significantly in the intervention group compared to the control group in the mean number of chronic medications, STOPP Frail Criteria, MRCI and the 28-day cost of regular medications (p < 0.05) between admission and discharge. As for the PCP effect on the control and the intervention group at the end-stage organ failure, we did not observe statistically significant differences. On the other hand, when the effect of the PCP model on different degrees of frailty was evaluated, no unequal behavior was observed.