Background Pancytopenia is a common hematological condition encountered in clinical practice. Because there is a wide variation in causes of pancytopenia even in different populations of the same geographical region, identifying the pattern of underlying etiologies is crucial for proper management. This study was conducted to evaluate the clinico-hematological profile and different etiologies of pancytopenia among adults presenting to a clinical hematology department at a tertiary care hospital of Western India. Methodology This observational study was conducted over a period of four years on 546 adult patients aged 18-93 years presenting with pancytopenia. After obtaining a detailed clinical history and physical examination, all participants were subjected to relevant investigations including bone marrow examination. Results A slight male preponderance was observed, and the most common age group (24%) was 21-30 years. Pallor was the most common clinical feature, followed by generalized weakness and fever. The most common cause of pancytopenia was acute leukemia (17.9%), followed by megaloblastic anemia (15.4%), aplastic anemia (11.0%), hypersplenism (7.8%), multiple myeloma (6.6%), and myelodysplastic syndrome (5.3%). Conclusions Acute leukemia was observed to be the most common cause of pancytopenia in this study, which is in contrast to various other studies from India conducted in different departments. Identification of etiologies of pancytopenia among patients attending hematology departments in various regions is expected to be useful in formulating diagnostic algorithms and management strategies, which can help clinicians to better manage such patients.