Background This study investigates a broad spectrum of psychiatric disorders, substance use disorders, gambling, and internet gaming disorders in Swedish 18-year-old boys and girls with the aim of estimating the prevalence of disorders and comorbidity. Methods We used a two-phase design with screening to detect candidates for clinical interviews. Screening included 949 adolescents (55.6% girls), out of which 758 adolescents (57.0% girls) were selected for interview with at least one of four instruments: M.I.N.I., ADDIS, NODS and IGDS. Of these, 387 (61.2% girls) were interviewed. Gender separated prevalence was estimated on the assumption that those selected but not interviewed had the same distribution as those interviewed based on similar outcomes above screening cut-offs. Comorbidity between types of disorders was estimated on similar assumptions. In addition, comorbidity between dyads of the ten most common specified disorders was calculated based on recorded data without these assumptions. Results We estimated that 14.6% met the criteria of a substance use disorder (SUD), mostly concerning alcohol and more frequent in girls than in boys. Those meeting the criteria lifetime of at least one of 16 other psychiatric disorders were 26.7%, more than twice as frequent in girls compared to boys, and with depression being the most common disorder. Gambling and gaming disorders were found almost exclusively in boys, of which 5.8% met the criteria for gambling, and 2.3% for gaming disorders. Of girls with a SUD, 40% also had a psychiatric disorder, while on the other hand more than 28% of girls with a psychiatric disorder also had a SUD. In boys with a SUD, 22% had another psychiatric disorder, while 15% of those with a psychiatric disorder also had a SUD. Conclusions Psychiatric comorbidity is common in SUDs in adolescents, which calls for screening and diagnostic efforts in young patients presenting with symptoms of SUDs. Girls with SUDs are at higher risk of also suffering from psychiatric conditions. Gambling and gaming disorders appear in a substantial minority of adolescents and warrant further study of their comorbidity. Since prevalences and comorbidity were estimated on the assumptions mentioned, some caution in interpreting the results is needed.