This study aims to: 1.to describe the drug utilization (socio-demographic, clinical features, type, dosage, indication at the time of opioid therapy initiation) of the different opioids as well as to study the persistence of these drugs among subjects aged ≥ 18 years old in Catalonia, Spain, 2. to assess and compare the risk of pre-specified adverse events first between incident users of opioids and then compared to non-opioids pain-killers, 3. to study the association between long-term use of opioids compared to paracetamol. Methods: population-based cohort study (www.SIDIAP.org). Inclusion criteria: all new users of study drugs (no use in previous year) between 2007-2016, ≥18 years old and with ≥1 year of valid data. Follow-up: (latest of) start of the study period, 1-year of valid data until (earliest of) end of enrolment, discontinuation, date of last capturing data or event of interest. Outcomes: 1. opioids and non-opioid (NSAIDs, Cox-2 inhibitors, paracetamol, metamizole, aspirin) exposure. Variables: Socio-demographic, BMI, Charlson comorbidity index (CCI), frailty, cognitive and quality of life indexes, opioid use (type/dosage), prescriber and indication, 2. cardiovascular events (myocardial ischemia, stroke, heart failure and arrhythmia), fractures, falls, sleep and gastro-intestinal disorders, opioid dependence/abuse, all-cause mortality. Confounders: socio-demographic and socioeconomic status (MEDEA), medical conditions, CCI, surgeries and drugs (hypnotics, benzodiazepines, SSRI, anticonvulsant), number of different ATCs prescribed, GP visits, hospital admissions, falls and traffic accidents. Statistics: Kaplan Meier plots for drug persistence. Propensity score analysis and Cox regression model to estimate the relative risk according to drug use.