Problem: The prescription opioid epidemic in the United States is associated with negative health and social outcomes. Examining the association of socio-demographic predictors, BMI, suicidal behavior and health services use in prescription opioid use without misuse (POU), prescription opioid misuse without use disorders (POMU) and prescription opioid use disorder (POUD) samples is important to make necessary intervention in each sample to prevent the expansion of epidemic. Method: A cross-sectional secondary data analysis using the 2016-2017 National Survey on Drug Use and Health (NSDUH) data was conducted. The sample size for the past year POU was 24,400; POMU was 3,771; POUD was 721 and the reference sample who did not have any use of prescription opioid in the past year was 55,304. Result: The prevalence of the past year POU is 32.4 %, POMU is 5.2 % and POUD is 1.0 %. Age ≥ 50 and age 30-49 years have a higher risk of POU [OR 1.37; OR 1.44] and age ≥ 50 has a lower risk of POMU [0.54] than age 18-29 years. Males have a lower risk of POU [0.92] and a higher risk of POMU [1.31] and POUD [1.66] than females. Non-Hispanic Whites have a higher risk of POU [1.33], POMU [1.42] and POUD [3.68] than Hispanics. Single people have a higher risk of POMU [OR 1.27] than married individuals. ‘Medicaid only’ insurance coverage has a higher risk of POU, POMU, POUD than almost all other insurance types. Obesity [OR 1.45] and overweight [OR 1.18] have a higher risk of POU than normal BMI. Suicidal behaviour has a higher risk of POU [1.25] < POMU [2.58] < POUD [3.37]. More than 1 emergency department visit has a higher risk of POMU [2.10] < POU [2.22] < POUD [3.74]; more than 1 overnight hospital stay has a higher risk of POMU [1.40] < POUD [1.70] < POU [2.03] ; more than 1 outpatient department visit has a higher risk of POMU [1.29] < POUD [1.43] < POU [2.38] and mental health services use has a higher association with POU [1.49] < POMU [1.90] < POUD [4.34] when compared with no use of those facilities. Conclusion: This research has identified significant risk factors of POU, POMU, and POUD in the US adult population, and recommended intervention measures to reduce the burden of the prescription opioid epidemic in the US.