Background: Drug therapy in the elderly needs an emphasis on age-related changes in drug pharmacokinetics and pharmacodynamics profile. Hospitalized elderly patients are at risk of more than one disease and polypharmacy associated with these; they are at risk of drug-related problems. This study aimed to assess the role of clinical pharmacy on identifying and resolution of drug-related problems among elderly patients admitted to medical ward of Northwest Ethiopia comprehensive specialized hospitals. Methods: A multicenter prospective observational study was conducted. A systematic sampling technique was used. The identified drug-related problem was recorded and classified using Cipolle, and adverse drug reaction was assessed using Naranjo algorithm of adverse drug reaction probability scale, and Medscape was used for drug-drug interaction. Data were analyzed by using STATA software version 14.1. Logistic regression was used, and results were reported as odds ratios (ORs) with 95% Confidence intervals with P value < 0.05 statistically significant. Result: A total of 389 study participants were included in the study. About 266 (68.4%) of the participants had at least a single drug-related problem. About 503 drug-related problems were identified with a mean of 1.32 (CI: 1.27-1.36) drug-related problem per patient. The three-leading categories of drug-related problems were dose too high 108 (21.5%), nonadherence 105 (20.9%), and adverse drug reaction 96 (19.1%). Alcohol use (AOR = 2.2, 95CI%: 1.23-3.94), source of the drug (AOR = 2.85, 95CI%: 1.63-4.98), length of hospitalization (AOR = 2.32, 95CI%: 1.37-3.95), number of comorbidities (AOR = 1.48, 95CI%: 1.09-1.99), and polypharmacy (AOR = 3.06, 95CI%: 1.72-5.46) were important risk factors for drug-related problems. From the intervention provided, 84.7% were accepted by prescribers. Among the total drug-related problems 67.4% of the problem was totally solved. Conclusion: This study revealed that DRPs were high among elderly patients admitted to medical ward of Northwest Ethiopia. Comorbidity, length of hospitalization, ploy-pharmacy, payer, and alcohol drinker were more likely to developed drug-related problems. Treatment optimizations were also done by clinical pharmacists and interventions were well accepted by prescribers.