Background Adherence to oral anticancer medication is important in cancer chemotherapy, with the advent of many oral anticancer regimens to ensure adequate cytologic response. Literature on adherence to oral anticancer therapy in India is very less. Materials and Methods This is a cross sectional analytical study consisting of all fit patients > 18 years of age taking oral anticancer therapy, with or without intravenous (IV) chemotherapy. Adherence was determined using Morisky-Green-Levine (MGL) scale, and factors affecting adherence details about cancer and treatment were obtained. All fit patients were recruited. Information was obtained using Tamil questionnaire and pro forma. Observation Of 152 patients, only 111 patients were found to be adherent to treatment. The mean age of the study population was 49.03 13.48 years. Only 12.5\% of patients were aware of the diagnosis, treatment, and outcome. The study population consisted mainly of patients with chronic myeloid leukemia, colorectal carcinoma, breast carcinoma, and stomach carcinoma, which amounted for 78.3\% of the study population. Bivariate analysis concluded that duration of treatment, adverse drug reaction (ADR), duration of oral anticancer drug intake in a month, coadministration with IV anticancer drugs, and frequency of drug intake (anticancer drug) were significant factors affecting drug adherence. Multivariate analysis of the above variables was insignificant, but ADR tended toward significance. Conclusion Drug adherence plays a major role in treatment outcome in cancer patients. ADR was independently associated with decreased drug adherence. Key interventions which should include counseling and behavioral modifications will reduce nonadherence.