Background The efficacy and safety of anti-retroviral treatment is affected by many factors and compliance is key in therapy success. A lack of adherence may lead to therapeutic failure and higher rates of drug resistance. PurposeTo describe collected data about outpatient antiretroviral treatment adherence and analyse characteristics and factors associated with the non-adherent population. Materials and Methods A retrospective observational study was conducted over 27 months on all outpatients on antiretroviral therapy who attended our hospital for human immunodeficiency virus (HIV) monitoring between June 2010 and September 2012. Each patient’s adherence was checked and recorded every 6 months. This was measured as ‘(Total no. of units dispensed/Total no. of units needed) × 100’. Those patient with adherence >95% were considered as ‘adherent’ and those with <95% as ‘non-adherent’. All results were recorded in a database. For the ‘non-adherent’ population the following features were reviewed: Sex, age, drug use, presence of Hepatitis B (HBV) or Hepatitis C (HCV) and total number of tablets/day, including drugs for other diseases besides HIV. Results During the period of study, 1841 adherence cheques were made on a total of 630 patients (2.9 tests/patient). 24.6% of the HIV patients in treatment were non-adherent in at least one cheque. Their average age was 45.5 ± 8.6 years, 74% men, mean treatment duration of 8 ± 4.4 years, and a median consumption per day of 4 doses (range 1 to 16). 35.5% of these patients took drugs, 7.1% were co-infected with HBV and 45.2% were co-infected with HCV (5.2% was co-infected with both viruses). The Chi-square test showed a significant relationship (p < 0.05) between substance abuse, HCV infection and male gender in non-adherent patients. Conclusions The study revealed a large percentage of non-adherent patients who compromised the effectiveness of their antiretroviral treatment. The intervention of hospital pharmacists, checking on compliance and following up with patients, could play an important role in reducing this negative factor, especially in those with HCV and/or substance abuse. No conflict of interest.