OBJECTIVES:  Today, Complementary and alternative medicine (CAM) use is being routinely practiced by cancer patients worldwide. However, researches on CAM use by cancer patients are scarce in Ethiopia. This study aimed at assessing the prevalence and modes of CAM use as well as comparing quality of life (QoL) in CAM users and non-users among cancer patients receiving chemotherapy at university of Gondar referral hospital (GURH), northwest Ethiopia. METHODS:  A cross sectional study was employed on 395 cancer patients receiving chemotherapy at GURH chemotherapy center. A questionnaire about the socio-demographic, disease characteristics as well as CAM use was filled by the respondents. The European Organization for Research and Treatment of Cancer core QoL (EORTC QLQ-C30) questionnaire was employed to evaluate QoL among CAM users and non users. Descriptive statistics, univariate and multivariate logistic regression analysis were used to analyze/come up with the prevalence and correlates of CAM use. RESULTS: More than two third of the respondents, 78.9%, were reported to be CAM users. Educational status, average monthly income, disease stage and co morbidity were found to be strong predictors of use of CAM. The commonly utilized types of CAM were traditional herbal based medicine, special foods and spiritual healing. Only 20.8% of patients discuss with their doctors about CAM use. No significant difference were found in QoL between CAM users and non users except in financial difficulties, where CAM users (54.86±4.67) had significantly higher mean scores in financial difficulties than non users (46.27±3.71) (p = 0.020). CONCLUSIONS:  The patients’ higher magnitude of CAM use along with very low disclosure rate to their health care providers can have a marked potential to cause ineffective cancer management and adverse effects. Health care providers should be open to discuss the use of CAM with their patients as it will lead to better health outcome.