Purpose: This study assessed the awareness, actions, and predictors of actions on adverse drug reaction reporting among patients attending a referral hospital in southern highland Tanzania. Methods: A hospital-based cross-sectional study was from January to August 2022 at Mbeya Zonal Referral Hospital (MZRH) in Mbeya, Tanzania. A total of 792 adult patients with chronic conditions attending outpatient clinics at MZRH were recruited consecutively. A semi-structured questionnaire was used to collect demographic characteristics, ADR awareness, and actions when encountering ADR. Data were analyzed using the statistical package for social sciences (SPSS) version 23 and results are summarized using frequency and percentages. Binary logistic regression was used to assess the predictors associated with reporting ADR among patients. P-value ≤ 0.05 was considered statistically significant. Results: Out of 792, 397(50.1%) were males and 383(48.4%) had a primary education level. Only 171(21.6%) participants previously experienced ADR and 111(14.1%) were aware that ADR is an unexpected harm that occurs after medication use. The majority 597(70.3%) of the participants said will report ADR to healthcare providers, 706(88.9%) prefer reporting ADR to healthcare providers and 558(69.1%) said patients are not aware of the importance of reporting ADR. Patients aged below 65 years of age, unemployed ((AOR (95%CI) =0.4(0.18 – 0.87), self-employed ((AOR(95%CI) =0.5(0.32 – 0.83)), and those who ever encountered ADR ((AOR(95%CI) =0.1(0.05 – 0.11)), were more likely to report the ADR to HCPs compared to the rest. Conclusions: The majority of patients are not aware of what is ADR and the importance of ADR reporting. Most of the patients prefer to report ADR to healthcare providers. We recommend an awareness campaign to raise awareness of the patients on ADR and other methods of ADR reporting.