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The aim of the present study was to observe adverse drug reactions (ADRs) with respect to polypharmacy at tertiary care centre at Bastar, Jagdalpur (Government Medical College, Jagdalpur). A prospective, observational evaluation of the ADRs conducted over a period of 6 months in Department of Medicine in Government Medical College, Jagdalpur. During the study period, a total of about 4850 patients visited the OPD and inpatient ward of medicine department, and 154 ADRs events were reported. Out of 154 reports that were identified, a higher percentage of ADRs in females (51.29%) was observed as compared to males (48.7%). Of the 154 ADRs, 76 (49.35%) were found to be mild, 55 moderate (35.71%), and 23 severe (14.93%). A total of 99 (64.28%) ADRs were observed in patients receiving four or more medications concurrently. Conversely 55 (35.71%) ADRs were detected in patients using three or less medicines. The largest number of reports was associated with antimicrobial therapy (28.57%), followed by antihypertensive (24.02%) and antidiabetics (14.28%). Among the affected organ systems, gastrointestinal ADRs constituted a major component (39.61%) followed by skin reactions (28.57%). On causality assessment, nearly 36.36% ADRs were considered as probable, 31.16% possible, and 9.74% could not be categorized and were placed under unassessable. Expected, limited ADR are permissible in normal clinical setting, but the present study focuses on the result showing increased and amplified ADR associated with the polypharmacy practices, which may be curtailed with rational drug prescribing habit. [ABSTRACT FROM AUTHOR]