Introduction In Ethiopia the pharmacy service has had several gaps among these were low patient satisfaction, and poor availability of essential pharmaceuticals. In addition, previous studies showed variation in magnitude of client satisfaction, and there is no previous study in the study area. Therefore, the aim of the study was to determine client satisfaction with outpatient pharmacy service and associated factors among adult clients at Dubti General Hospital in Afar, Ethiopia. Methods A hospital based cross sectional study design was employed from February 1 to March 30, 2020 at Dubti General Hospital. Participants were selected by systematic random sampling method. Bivariate and multivariate binary logistic regression was computed to assess statistical association between the outcome variable, and independent variables. AOR with 95% CI were used to show statistical Significance at P <0.05. Results The overall satisfaction towards outpatient pharmacy service was 165(40.5%). Regarding associated factors, service payment insured through their workplace was positively associated with satisfaction (AOR = 3.178, 95% CI: 1.294–7.80) where as availability of some medications (AOR = 0.393, 95% CI: 0.208–0.741), unfair medication cost (AOR = 0.613, 95% CI: 0.607–0.910), and lack of organized pharmacy work flow (AOR = 0.105, 95% CI: 0.049–0.221) were negatively associated with clients’ satisfaction. Conclusion The clients’ satisfaction in this study is low that warrants immediate corrective measures. Corrective measures should be taken based on identified gaps such as improving drug availability, pharmacy work flow, and cost of medications.