Abstract Objective and motivation Time-of-flight (TOF) tomography used by a clinical ultrasound tomography device can efficiently and reliably produce sound–speed images of the breast for cancer diagnosis. Accurate picking of TOFs of transmitted ultrasound signals is extremely important to ensure high-resolution and high-quality ultrasound sound–speed tomograms. Since manually picking is time-consuming for large datasets, we developed an improved automatic TOF picker based on the Akaike information criterion (AIC), as described in this paper. Methods We make use of an approach termed multi-model inference (model averaging), based on the calculated AIC values, to improve the accuracy of TOF picks. By using multi-model inference, our picking method incorporates all the information near the TOF of ultrasound signals. Median filtering and reciprocal pair comparison are also incorporated in our AIC picker to effectively remove outliers. Results We validate our AIC picker using synthetic ultrasound waveforms, and demonstrate that our automatic TOF picker can accurately pick TOFs in the presence of random noise with absolute amplitudes up to 80% of the maximum absolute signal amplitude. We apply the new method to 1160 in vivo breast ultrasound waveforms, and compare the picked TOFs with manual picks and amplitude threshold picks. The mean value and standard deviation between our TOF picker and manual picking are 0.4 μs and 0.29 μs, while for amplitude threshold picker the values are 1.02 μs and 0.9 μs, respectively. Tomograms for in vivo breast data with high signal-to-noise ratio (SNR) (∼25 dB) and low SNR (∼18 dB) clearly demonstrate that our AIC picker is much less sensitive to the SNRs of the data, compared to the amplitude threshold picker. Discussion and conclusions The picking routine developed here is aimed at determining reliable quantitative values, necessary for adding diagnostic information to our clinical ultrasound tomography device – CURE. It has been successfully adopted into CURE, and allows us to generate such values reliably. We demonstrate that in vivo sound–speed tomograms with our TOF picks significantly improve the reconstruction accuracy and reduce image artifacts.