Aim: To identify clinical and genetic factors associated with outcome of opioid treatment. Patients & methods: We performed an exploratory analysis in a cohort of 353 patients treated with fentanyl, morphine, oxycodone and/or hydromorphone for cancer-related pain, exploring selected clinical and pharmacogenetic factors for a correlation with treatment failure for all and per type of opioid. Results: Use of adjuvant pain medication, intensity of pain at rest and age were associated with treatment failure in the various cohorts. Only the genetic variants rs12948783 (RHBDF2) and rs7016778 (OPRK1) correlated statistically significant in univariate, but not in multivariable analysis. Conclusion: Several clinical and genetic factors were identified that warrant further study to clarify their role and use in opioid treatment.