Nurses play a functional role in preventing drug related problems. They need to be aware of the dangers of polypharmacy while reviewing patient medications. We studied the nurses' opinion on the diverse effects of polypharmacy in the hospital setting. Nurses working in a tertiary care teaching hospital participated in this cross-sectional study, conducted over 3 months, by responding to a self-administered questionnaire. Chi-square test was used to analyze association between socio-demographic characteristics and items in the study. A value of P<0.05 was considered statistically significant. Increased drug interactions scored the highest (98.1%), followed by increased adverse drug effects (81.9%), and increase in financial burden (69.5%) among the negative effects of polypharmacy. 61% of the respondents felt that polypharmacy increased therapeutic effect in polypathology. No difference was observed in the opinion between male and female nurses or among varying nursing experience. Nurses with 5-10 years of experience opined increase in non-compliance to prescribed medication regimen and increase in financial burden also as negative attributes. Nurses pointed out both positive and negative implications of polypharmacy. Training programs such as continuing nursing education and workshops can be planned to translate this knowledge into practice in their routine nursing practice.