Background <p>The decision to administer opioids for dyspnea caused by heart failure should be made on an individual basis. However, factors associated with the effectiveness of opioids remain unclear, and information that could guide this decision is lacking. This study aimed to explore factors associated with the effectiveness of opioids to relieve dyspnea caused by heart failure.</p> Methods <p>This retrospective, multicenter, observational study included patients 18 years of age or older at the time of admission who received opioid administration (morphine, oxycodone, or hydromorphone) for dyspnea relief but did not receive invasive ventilatory support during hospitalization. Data were collected from the medical records.</p> Results <p>A total of 129 cases (30 ineffective cases, 80 effective cases, and 19 cases with missing dyspnea assessment data) were collected. The multivariable logistic regression analysis results indicated that the odds ratios of the New York Heart Association classification, number of diuretics used, and oxygen flow rate associated with the presence or absence of dyspnea improvement attributable to opioid administration were 0.496 (95% confidence interval, 0.254–0.967), 1.506 (95% confidence interval, 1.131–2.007), and 0.974 (95% confidence interval, 0.923–1.027), respectively. Trends in odds ratios for both the number of diuretics used and New York Heart Association classification were preserved in the multivariable logistic regression model that included factors that potentially influence dyspnea (<i>p</i> &lt; 0.05).</p> Conclusion <p>The effectiveness of opioids for relieving dyspnea caused by heart failure in hospitalized patients was positively associated with the number of diuretics used and negatively associated with the New York Heart Association classification.</p>