BackgroundLower limb amputation can have profound physical, psychological, and social effects on individuals. Assistive aids like prosthetic lower limbs can help an individual regain mobility and thereby affect their self‐esteem and quality of life.ObjectiveTo assess self‐esteem and quality of life in patients with transtibial amputations who are using a transtibial prosthesis and explore the association between sociodemographic and amputation‐related factors with self‐esteem and prosthesis‐related quality of life measures.DesignA cross‐sectional study.SettingAn orthotics and prosthetics center (Bhagwan Mahaveer Viklang Sahayata Samiti) in Jaipur, Rajasthan.ParticipantsPatients with transtibial amputations using exoskeletal prostheses between July and September 2022, in Jaipur, Rajasthan.Main Outcome MeasuresThe study used Rosenberg self‐esteem questionnaire and Prosthesis Evaluation Questionnaire (PEQ) for self‐esteem and quality of life assessment, respectively. Descriptive analysis was used to present the demographic details, and nonparametric tests examined the relationship between PEQ dimensions and sociodemographic variables.ResultsThe study included 138 participants, primarily <40 years old (45.7%) and mostly engaged in high‐activity occupations. Self‐esteem mean score (SD) was 19.9 (3.9), with 89.1% exhibiting normal self‐esteem. Prosthesis‐related quality of life, showed high satisfaction across various domains, including ambulation, appearance, frustration, perceived response, residual limb health, social burden, sounds, utility, and well‐being. No significant associations were found between sociodemographic factors, amputation‐related variables, and self‐esteem. However, PEQ scales showed associations with gender, age, occupation, type of amputation, and years of prosthesis use.ConclusionThese results highlight the potential advantages of exoskeletal prostheses in improving the standard of living for people with transtibial amputations. Further research is essential to develop targeted interventions for improving their overall quality of life.