The aim of this study was to investigate the effect of Pivotal Response Treatment versus robot-assisted Pivotal Response Treatment on self-initiations of children with autism spectrum disorder and to explore the relation between self-initiations and collateral gains in general social-communicative skills. Forty-four participants with autism spectrum disorder aged 3–8 years (Pivotal Response Treatment: n = 20, Pivotal Response Treatment + robot: n = 24), who were recruited as part of a larger randomized controlled trial (number NL4487/NTR4712, https://www.trialregister.nl/trial/4487 ), were included. Self-initiations were blindly coded, assessing video probes of all parent–child sessions using an event-recording system. General social-communicative skills were assessed with the parent- and teacher-rated Social Responsiveness Scale during intervention and at 3-month follow-up. Results using linear mixed-effects models showed overall gains in self-initiations during both Pivotal Response Treatment intervention groups (estimate = 0.43(0.15), 95% confidence interval (CI): 0.13–0.73), with larger gains in functional self-initiations in children receiving robot-assisted Pivotal Response Treatment (estimate = −0.27(0.12), 95% confidence interval: −0.50 to −0.04). Growth in self-initiations was related to higher parent-rated social awareness at follow-up compared with baseline in the total sample ( r = −0.44, p = 0.011). The clinical implications of these findings, as well as directions for future research in the utility of Pivotal Response Treatment and robot assistance in autism spectrum disorder intervention, are discussed. Lay abstract The initiation of social interaction is often defined as a core deficit of autism spectrum disorder. Optimizing these self-initiations is therefore a key component of Pivotal Response Treatment, an established intervention for children with autism spectrum disorder. However, little is known about the development of self-initiations during intervention and whether this development can be facilitated by robot assistance within Pivotal Response Treatment. The aim of this study was to (1) investigate the effect of Pivotal Response Treatment and robot-assisted Pivotal Response Treatment on self-initiations (functional and social) of young children with autism spectrum disorder over the course of intervention and (2) explore the relation between development in self-initiations and additional gains in general social-communicative skills. Forty-four children with autism spectrum disorder (aged 3–8 years) were included in this study. Self-initiations were assessed during parent–child interaction videos of therapy sessions and coded by raters who did not know which treatment (Pivotal Response Treatment or robot-assisted Pivotal Response Treatment) the child received. General social-communicative skills were assessed before start of the treatment, after 10 and 20 weeks of intervention and 3 months after the treatment was finalized. Results showed that self-initiations increased in both treatment groups, with the largest improvements in functional self-initiations in the group that received robot-assisted Pivotal Response Treatment. Increased self-initiations were related to higher parent-rated social awareness 3 months after finalizing the treatment.