Introduction: The SARS-CoV-2 pandemic generated the need to keep immunosuppressed patients away from hospital institutions for as long as possible. This in turn stimulated the implementation of a home hospitalization model for autologous hematopoietic stem-cell transplantation (HSCT). Purpose: To analyze whether there are significant differences in post-transplantation complications related to catheters observed in patients treated in the home-transplant care modality compared to patients treated in the hospital. Methodology: Observational, analytical, longitudinal, and retrospective study of cases and controls. A convenience sample was chosen, in which the cases comprised 20 patients included in the home HSCT care model. For each patient, it was considered suitable to propose two controls among those who received autologous transplantation in the last five years with a baseline demographic and pathological profile similar to the case for whom they were control. Results: The home patients achieved an average of 22.4 ± 2.6 days of evolution with an average of 16.4 ± 2.08 days post-transplant, compared to the hospital process with an average of 21.21 ± 4.18 days of evolution and 15.51 ± 3.96 days post-transplant (evolution days p = 0.022; post-transplant days p = 0.002). A higher percentage of use of parenteral nutrition (p = 0.036) and transfusions (p = 0.003) was observed during the post-transplant phase in the hospital. The rest of the therapeutic measures did not show significant differences. When analyzing the frequency of adverse effects in the post-transplant phase, a significant increase in neutropenic fever (OR = 8.55) and positive blood cultures (OR = 6.65) was observed in hospital patients. Any other significant differences in other variables related to PICC were found (presence and days of neutropenic fever, catheter infection, complications, pathogens, admission to the ICU, or death). Concerning local complications (pain, DVT, Medical adhesive-related Skin Injury, and erythema), there was more erythema in the hospital (p = 0.056). Conclusions: The results obtained indicate that regarding the appearance of complications associated with PICCs in home hospitalization HSCT patients, there are no significant differences compared to hospitalization, so that home care can be a safe context for people with these lines