Psychiatric comorbidities and use of psychotropic medications are common among patients with autism spectrum disorder (ASD). However, most previous research used data from the United States (US) and few studies have compared medication use in ASD to control groups, making contextualization of results difficult. In the United Kingdom (UK), general practitioners play a key role in the management of ASD. We conducted a retrospective, cross-sectional study over calendar year 2015, using primary care data from the UK. We identified a prevalent cohort of ASD cases (n = 10,856) and matched control groups of (a) general population (n = 21,712) and (b) attention deficit hyperactivity disorder (ADHD; n = 7,058) on age, sex and region. We described psychiatric comorbidities, psychotropic medications, and healthcare utilization in all three cohorts. Within the ASD cohort, we used multivariable logistic regression models to explore associations between patient characteristics and the outcomes of: any psychotropic medication, polypharmacy, and number of primary care visits. We used conditional logistic regression to compare the ASD and control groups. Psychiatric comorbidities were recorded for 41.5% of ASD patients; 32.3% received psychotropic medication and 9.8% received polypharmacy. Increased age and all psychiatric comorbidities (except conduct disorder) were associated with treatment use. Males were less likely to receive a treatment than females [Odds ratio (OR) 0.74 (0.66-0.83)]. ASD patients were more likely to take psychotropic medications than the general population ], but less likely compared to ADHD patients ]. Overall, rates of medication use in the UK were lower than those previously reported in the US.Lay Summary: We used electronic medical records from the UK, to describe the amount of psychiatric comorbidities, psychotropic medication use and healthcare resource use in ASD. Around one in three people with ASD were prescribed a psychotropic medication, which was more than the general population, but less than for those with ADHD. Increased age, psychiatric comorbidities and female gender were all independently associated with psychotropic medication use. Rates of medication use in the UK were lower than those previously reported in the US.