Autism spectrum disorder (ASD) is often accompanied by self-injurious behavior (SIB), aggression, and tantrums, symptoms that have reportedly improved with micronutrient (vitamins and minerals) treatment. The current study took advantage of naturally occurring differences in parental preferences for treatment approaches. The micronutrient group asked for treatment without pharmaceuticals (n = 44, aged 2-28 years at entry [M = 8.39 +/- 5.58]). Their records were matched with those of 44 similar children whose families requested conventional treatment (medication group). Both groups improved on both the Childhood Autism Rating Scale and the Childhood Psychiatric Rating Scale (all p values <0.0001). Both groups also exhibited significant decreases in total Aberrant Behavior Checklist scores, but the micronutrient group’s improvement was significantly greater (p < 0.0001). SIB Intensity was lower in the micronutrient group at the end of the study (p = 0.005), and improvement on the Clinical Global Impressions scale was greater for the micronutrient group (p = 0.0029). It is difficult to determine whether the observed changes were exerted through improvement in mood disorder or through an independent effect on autistic disorder. There were some advantages to treatment with micronutrients-lower activity level, less social withdrawal, less anger, better spontaneity with the examiner, less irritability, lower intensity SIB, markedly fewer adverse events, and less weight gain. Advantages of medication management were insurance coverage, fewer pills, and less frequent dosing.