Background: Cancer patients often receive multiple drugs to maximize their therapeutic benefit, treat co-morbidities and counter the adverse effects of chemotherapy. Concomitant administration of multiple drugs increases the risk of drug interactions leading to compromised therapeutic efficacy or safety of therapy. The purpose of this study was to identify the prevalence, levels and predictors of potential drug-drug interactions (pDDIs) among cancer patients. Methods: Six hundred and seventy-eight patients receiving chemotherapy from two tertiary care hospitals were included in this study. Patient medication profiles were screened for pDDIs using the Micromedex® database. Logistic regression analysis was performed to identify the predictors of pDDIs. Results: The overall prevalence of pDDIs was 78%, majority of patients had 1-2 pDDIs (39.2%). A total of 1843 pDDIs were detected. Major-pDDIs were most frequent (67.3%) whereas, a significant association of pDDIs was found between >7 all prescribed drugs (p <0.001) and ≥3 anti-cancer drugs (p <0.001). Potential adverse outcomes of these interactions include reduced therapeutic effectiveness, QT interval prolongation, tendon rupture, bone marrow suppression and neurotoxicity. Conclusions: Major finding of this study is the high prevalence of pDDIs signifying the need of strict patient monitoring for pDDIs among cancer patients. Patients at higher risk to pDDIs include those prescribed with >7 any types of drugs or ≥3 anticancer drugs. Moreover, list of most frequently identified major and moderate interactions will aid health care professional in timely identification and prevention of pDDIs.