Context: Stenotrophomonas maltophilia is a known nosocomial pathogen which is intrinsically resistant to multiple antibiotics. In India, S. maltophilia infection has only few case reports. Aim: To determine the incidence of S. maltophilia infection from clinical isolates based on the specimen type, antibiotic susceptibility pattern, and impact on outcome. Settings and Design: One-year retrospective study was done at a tertiary liver care center. Methods: Patients with S. maltophilia isolation in clinical samples were selected. Serial levels of serum procalcitonin and total leukocyte count were recorded. Environmental surveillance was done from the wards of S. maltophilia isolation as part of routine practice. Statistical Analysis: Continuous data were compared using Kruskal–Wallis test/Mann–Whitney test. The categorical data were compared by Chi-square/Fisher's exact test, wherever necessary. Besides this, an appropriate analysis like survival was carried out at the time of data analysis. Results: One hundred isolates were obtained from eighty patients of six wards. The greatest number (44/100, 44%) were from the Liver Coma Intensive Care Unit and the lowest (3/100) from the day care. Isolation from the respiratory samples was 1.32% and bloodstream infection 0.6%. Of 100 isolates, 12 (12%) were resistant to both trimethoprim–sulfamethoxazole and levofloxacin. Conclusion: S. maltophilia was effectively isolated from the hospital environment, with two of hand impression and three of water samples' positive. Patients with respiratory infection had most S. maltophilia isolates. Antibiotic susceptibility revealed more resistance than reported in this region.