Objective: Serious games (SGs) are a promising means of fostering socio-emotional skills in children with autism spectrum conditions (ASC). However, alexithymia and emotional empathy have not yet been addressed adequately, and there is a lack of randomized controlled trials (RCT) to investigate skill maintenance and the transfer to functional behavior. Method: The manualized, parent-assisted SG Zirkus Empathico (ZE) was tested against an active control group, in a six-week multicenter RCT. Eighty-two children aged 5-10 years with ASC were assessed at baseline, post-treatment, and three-month follow-up. Parent-rated empathy and emotion recognition skills were defined as the primary outcomes. The secondary outcomes included measures of emotional awareness, emotion regulation, autism social symptomatology (Social Responsiveness Scale), and subjective therapy goals. Results: Training effects were observed after the intervention for empathy (d = 0.71) and emotion recognition (d = 0.50), but not at follow-up. Moderate effects on emotional awareness, emotion regulation, and autism social symptomatology were indicated by the short and mid-term assessments. Parents reported treatment goal attainment and positive training transfer. Conclusion: While a six-week training with ZE failed to induce lasting changes in empathy and emotion recognition, it may be effective for improving emotion regulation and mitigate alexithymia and general autism symptomatology.